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Year : 2014  |  Volume : 8  |  Issue : 16  |  Page : 122-146  

Cytotoxicity of dietary flavonoids on different human cancer types

Non Government Organization Praeventio, Tartu, Estonia

Date of Submission01-Feb-2014
Date of Acceptance27-Mar-2014
Date of Web Publication10-Jun-2014

Correspondence Address:
Katrin Sak
NGO Praeventio, Naituse 22 3, Tartu 50407
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-7847.134247

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Flavonoids are ubiquitous in nature. They are also in food, providing an essential link between diet and prevention of chronic diseases including cancer. Anticancer effects of these polyphenols depend on several factors: Their chemical structure and concentration, and also on the type of cancer. Malignant cells from different tissues reveal somewhat different sensitivity toward flavonoids and, therefore, the preferences of the most common dietary flavonoids to various human cancer types are analyzed in this review. While luteolin and kaempferol can be considered as promising candidate agents for treatment of gastric and ovarian cancers, respectively, apigenin, chrysin, and luteolin have good perspectives as potent antitumor agents for cervical cancer; cells from main sites of flavonoid metabolism (colon and liver) reveal rather large fluctuations in anticancer activity probably due to exposure to various metabolites with different activities. Anticancer effect of flavonoids toward blood cancer cells depend on their myeloid, lymphoid, or erythroid origin; cytotoxic effects of flavonoids on breast and prostate cancer cells are highly related to the expression of hormone receptors. Different flavonoids are often preferentially present in certain food items, and knowledge about the malignant tissue-specific anticancer effects of flavonoids could be purposely applied both in chemoprevention as well as in cancer treatment.

Keywords: Diet, flavonoids, human cancers, prevention, treatment

How to cite this article:
Sak K. Cytotoxicity of dietary flavonoids on different human cancer types. Phcog Rev 2014;8:122-46

How to cite this URL:
Sak K. Cytotoxicity of dietary flavonoids on different human cancer types. Phcog Rev [serial online] 2014 [cited 2019 Aug 17];8:122-46. Available from: http://www.phcogrev.com/text.asp?2014/8/16/122/134247

   Introduction Top

Numerous edible plant-derived compounds have been linked to the chemoprevention and treatment of cancer. [1],[2],[3],[4],[5],[6],[7],[8],[9] For the past decades, much research has been developed in order to discover natural compounds with potential anticancer activity [6],[10],[11],[12] and several plant-derived agents (e.g., paclitaxel, docetaxel; vinblastine, vincristine; topotecan, irinotecan, etoposide, etc.) have been successfully used for cancer treatments. [13],[14],[15] Among the anticancer medications, 69% of drugs approved between 1940 and 2002 are either natural products or developed based on knowledge gained from natural products, [16],[17] a rate which is much higher than in other areas of drug development. [18] Natural products offer an untold diversity of chemical structures, and it is very likely that phytochemicals will continue to be important in cancer therapeutics. [19],[20],[21] Application of plants in the treatment of cancer seems to be inevitable, constituting the basis for modern medical science and providing a great source for new drugs. [22],[23]

Medicine and one's daily food are equally important in making a sick body well. [24] Diet is intimately linked to both the incidence and avoidance of many types of cancer [25] and dietary behavior has been identified as one of the most important modifiable determinants of cancer risk. [26] Strong and consistent epidemiological evidences suggest that a diet enriched with naturally occurring substances significantly reduces the risk for many cancers. [27],[28],[29],[30],[31] Indeed, the adoption of diets rich in vegetables and fruits, together with the maintenance of physical activity and appropriate body mass, could reduce the cancer incidence by 30-40%. [32],[33],[34] Moreover, several studies suggest that there is a decreased risk for different types of cancer among vegetarians. [35] Numerous classes of compounds present in fruits and vegetables are assumed to take the role of cancer-preventive agents. Among these compounds, flavonoids have been proven to be particularly important. [27],[29],[36]

   Flavonoids as potent anticancer agents Top

Flavonoids are naturally occurring polyphenolic metabolites distributed throughout the plant kingdom and found in substantial amounts in fruits, vegetables, grains, nuts, seeds, tea, and traditional medicinal herbs. [37],[38],[39] Within individual plants, flavonoids occur in every part but are usually concentrated in the leaves and flowers. [40] Flavonoids are edible plant pigments responsible for much of the coloring in nature. [41],[42]

Many of the different flavonoids are part of the regular human diet. Although they are nonessential dietary factors, [9] flavonoids are thought to be nutritionally valuable compounds, [43] being the key natural products that provide the most essential link between the diet and prevention of chronic disorders. One of the most investigated activities of flavonoids is their contribution to cancer prevention and treatment. [6]

Several thousand flavonoids are known to occur in nature, defined chemically as compounds containing a phenylchromanone structure (C6-C3-C6) with at least one hydroxyl substituent. [44],[45],[46],[47] Flavonoids can be further divided into flavonols, flavones, flavanols, flavanones, anthocyanidins, and isoflavonoids based on the saturation level and opening of the central pyran ring [15],[45],[48] [Figure 1].
Figure 1: Scheme of major flavonoid aglycones and their glycosides

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The daily human intake of flavonoids is quite different in amounts and classes due to various feeding habits of people from different regions and cultures. [25],[49] Reports of estimated daily consumption of flavonoids range from 20 mg/day to 1 g/day. [50] As the total flavonoid intake in Western countries is estimated at 23 mg/day, [51] humans consuming high fruit and vegetable diets may ingest up to 1 g of these compounds daily. [52],[53] No information is available about the content of flavonoids in the diet of vegetarians. [54],[55] The main food sources of major dietary flavonoids are presented in [Table 1].

As natural products, flavonoids are regarded as safe and easily obtainable, making them ideal candidates for cancer chemoprevention or associated agents in clinical treatment. [3],[43],[56] Almost all artificial agents currently being used in cancer therapy are highly toxic and produce severe damage to normal cells. [57],[58] The ideal anticancer agent would exert minimal adverse effects on normal tissues with maximal capacity to kill tumor cells and/or inhibit tumor growth. [12],[34] The lack of substantial toxic effects for long-term therapies and inherent biological activity of flavonoids make them ideal candidates for new therapeutics. [16],[59] Indeed, flavonoids have been shown to reveal cytotoxic activity toward various human cancer cells with little or no effect on normal cells, and this fact has stimulated large interest in developing of potential flavonoid-based chemotherapeutics for anticancer treatment. [60],[61]

Several observations have suggested that natural flavonoids have growth inhibitory effects on various kinds of cancer cells mediated by different molecular targets and acting through diverse metabolic pathways. [62],[63],[64] However, the precise mechanisms responsible for the antitumor effect of flavonoids are still not thoroughly understood. [64],[65] Flavonoids can easily bind to the cell membrane, penetrate in vitro cultured cells, and modulate the cellular metabolic activities. [66],[67] Mitigation of oxidative damage, inactivation of carcinogen, inhibition of proliferation, promotion of differentiation, induction of cell cycle arrest and apoptosis, impairment of tumor angiogenesis, and suppression of metastasis contribute to the anticarcinogenic activities of flavonoids. [24],[25],[30],[32],[49],[68] These polyphenolic compounds can interact with xenobiotics metabolizing enzymes, inhibit several kinases involved in signal transduction, interact with estrogen type II binding sites, and alter gene expression patterns. [61],[69],[70],[71]

Normal cell growth is maintained by the balance between cell proliferation and cell death, and apoptosis is a central regulator of tissue homeostasis. [72],[73] Cells from a variety of human malignancies have a decreased ability to undergo apoptosis in response to some physiological stimuli. Induction of apoptosis in malignant cells may therefore represent a promising approach to both chemoprevention and chemotherapy, and searching for agents that can specifically trigger apoptosis in tumor cells has become an attractive strategy in anticancer drug discovery. [38],[74],[75],[76],[77] The anticancer efficacy of flavonoids is due, at least in part to their ability to induce apoptosis of tumor cells. [37],[78],[79],[80],[81]

One of the most common incidents required for human cancer development known as a hallmark of malignant cells is deregulation of the cell cycle. [35],[82],[83] Agents that can inhibit cell-cycle progression and lead to cell-growth arrest are very important in cancer prevention and therapy studies, [35] and considerable attention has been paid to the ability of dietary flavonoids to inhibit cell-cycle progression. [82] Flavonoids have been found to arrest cell-cycle progression at either G 1 /S or G 2 /M boundaries by modulating of multiple cell cycle regulatory proteins. [69] Somewhat conflicting results have been reported with regard to the stage-specific arrest caused by one and the same compound, [59],[84] and several studies have indicated the ability of flavonoids to block the cell growth at more than one stage of the cell cycle. [85]

Due to the polyphenolic structure, flavonoids have been found to possess both anti- and prooxidant action. [86] While antioxidant effect and ability to scavenge reactive oxygen species (ROS) have been shown to account for most of the reported biological effects of phenolic compounds, several recent studies have revealed that anticancer activities of flavonoids may be mediated through prooxidant action. [49],[87] Cancer cells exhibit a higher and more persistent oxidative stress level compared to normal cells, rendering malignant cells more vulnerable to being killed by drugs that boost increased ROS levels, such as some flavonoids. [88],[89],[90],[91] Whether a flavonoid acts as anti- or prooxidant depends on its dose, cell type, and also culture conditions. [37],[90],[92]

The specific activity of flavonoids on cell function can also depend on their chemical structure. [93],[94],[95] The structures of the most common dietary flavonoids are presented in [Table 1]. Important factors affecting cytotoxic and/or antiproliferative activities of polyphenols include the saturation of the C 2 -C 3 bond and the position as well as the number and substitution of hydroxyl groups in the A and B rings. [69],[96],[97] However, even the minor modifications in the molecules can be responsible for strong variations in their activity, and flavonoids with very similar structures could not produce identical biological responses. [40],[97],[98],[99] Indeed, some authors have suggested that the anticancer capability of flavonoids cannot be predicted based on their chemical composition and structure, [61] and it is the reason why no structure activity relationships are analyzed in the present work.

   Obscurities limiting the use of flavonoids in cancer chemoprevention and treatment Top

Flavonoids have been found to exert cytotoxic activities only at relatively high doses, within the micromolar concentration range. [26],[82],[100] The amount of dietary flavonoids in plasma varies according to several parameters such as functional groups and daily intake. [101] However, achieving the plasma levels sufficient to reveal antiproliferative and cytotoxic effects may not be possible via oral administration. [9],[100] For example, results from human data have shown that a full glass of orange juice supplies about enough naringenin to achieve a plasma concentration of 0.5 μM; [102] a one-time consumption of approximately 550 g of grapefruit juice results in a mean peak plasma concentration of 6 μM naringenin; [103] the physiological dose of hesperetin attainable from drinking orange juice is in the range of 0.5-6 μM; [104] human plasma concentration of hesperidin reaches to 0.5 μM at 5-7 hours after ingestion of 0.5 liter of commercial orange juice providing 400 mg hesperidin; [8] typical plasma concentration of apigenin is within 10 nM range; [45] the concentration of chrysin in plasma after a single dose of 400 mg remains below 0.1 μM; [101] and maximal plasma levels of luteolin reaches to about 0.2 μM at 1-2 hours after oral administration. [31] In contrast, methoxylated flavonoids display up to 100-fold higher plasma concentrations on account of the reduced phase II conjugation reactions. [101] Higher plasma levels can be achieved through intravenous injection, [9],[100] and the plasma concentration of flavonoids may also be significantly increased by regular intake for a prolonged period. [45],[101],[105]

Despite encouraging preclinical results, the usability of flavonoids for chemoprevention has encountered only limited success, largely because of inefficient systemic delivery and bioavailability. [106],[107],[108] Flavonoids are most often found in plant materials in the form of glycosides (bound to sugars), which are better soluble in water than the respective aglycones. [47],[68],[109] Most of the glycosides resist acid hydrolysis in the stomach [45] and are deglycosylated by β-glucosidases in the small intestine. [69] The aglycones are further glucuronidated and sulphated by the intestinal mucosa and liver before release into the blood serum. [47],[68],[69] It is therefore likely that phytochemicals can accumulate in the small intestine and colon at levels greater than in plasma. [110] Bioavailability of flavonoids is determined by different factors, including the sugar moiety of the polyphenolic compound and its further metabolism by the gut microflora, [11] showing that different groups of flavonoids may have different pharmacokinetic properties. [111],[112] Moreover, considerable interindividual variation between humans can also influence the flavonoid metabolism, thus affecting the therapeutic action of polyphenolic compounds. [103] Furthermore, the anticancer activity would be related not only to the parent flavonoid ingested but also to its metabolites; therefore, identification and measurement of the physiological flavonoid conjugates are important to thoroughly understand the role of dietary polyphenols in human health. [31],[52],[69]

   Comprehensive analysis of cytotoxicity of flavonoids on human cancer lines from different origins Top

Flavonoids have been demonstrated to suppress proliferation of various cancerous cells. [69] However, not all polyphenolic compounds share the same antiproliferative activity; [113] and depending on their structure, flavonoids display differences in the sensitivity and selectivity toward tumor cells. [26],[97],[114] The sensitivities of cancer cells against flavonoids can be different depending on their derived tissues, [16],[115] indicating that the cytotoxicity induced by flavonoids might be related to selected cancer types. [30],[116] Even in the case of flavonoids with quite similar structures, there are compound-specific effects which are relevant to modulate particular biochemical processes so that the development of certain neoplasms could be differentially influential pointing to the tissue-specific cytotoxic action. [117],[118] The effectiveness of flavonoids may vary also because of the different disease etiologies. [119]

It is of interest of the current review article to determine whether the most common dietary flavonoids can exert some clear-cut preferences to certain tumor tissue types. In nature, different members of the flavonoid family are often preferentially present in some food items; [120] and knowledge about the malignant tissue-specific cytotoxic effects of flavonoids could be purposely applied both in the chemoprevention based on the genetic cancer risks and familiar anamnesis as well as in the cancer treatment. For this purpose, quantitative data characterizing the cytotoxic effects of different flavonoids on different human tumor cell lines were compiled from the literature sources, and statistical analysis to calculate the respective mean parameters was performed. IC 50 values as the flavonoid concentrations required to inhibit 50% of cell growth are the most common representative indexes of the dose-response curve, [121] and these parameters were also used in the current work. The mean cytotoxic constants of the most common dietary flavonoids on cancer cell lines derived from various organ sites are presented in [Table 2]. Cultured human malignant cell lines used for evaluating the cytotoxicity of these compounds are listed in [Table 3].

Paucity of data complicates the analysis

Despite the extensive investigation carried out with flavonoids in the past decades, there are still quite a few parameters available, characterizing quantitatively the efficacy of polyphenolic compounds on certain cancer types. In this way, the IC 50 values of flavonoids measured using the cells derived from malignant esophageal tissues are too scarce to reveal any certain specificity patterns. At the same time, data measured on bone cancer lines show only very low or even no cytotoxic activity of different flavonoids [Table 2].

Rather, few half-maximal cytotoxic parameters are available also for cell lines derived from human tumors of bladder, mouth, stomach, pancreas, and ovary. However, some activity patterns and tissue specificities of flavonoids can still be brought forth for these organ sites. In the case of bladder, cancer flavones apigenin and luteolin seem to be cytotoxically most active. Besides these two flavones, chrysin and flavonol kaempferol have also been reported to have antiproliferative activity and induce apoptosis in oral cavity cancer cells. Epithelium of the oral cavity can absorb the flavonoids directly, and should benefit for high levels of exposure to these dietary phytochemicals. [122]

Flavones apigenin, baicalein, luteolin, nobiletin, and tangeretin have shown to be the most effective flavonoids against carcinomas of stomach, whereas luteolin has even proposed to be a promising candidate agent for treatment of gastric cancer. [123]

In addition to some flavonols, such as quercetin, fisetin, and galangin, flavanone glycoside hesperidin also inhibits human pancreatic cancer cells, explaining why lime juice rich in hesperidin has been suggested to possess potential in the prevention of pancreatic cancer. [124]

The growth of human ovarian cancer cells cannot only be suppressed by several flavones including apigenin, baicalein, luteolin, and wogonin but also by flavonols quercetin and kaempferol. Kaempferol is a good candidate compound for chemoprevention of ovarian cancer; as in human studies, a significant 40% decrease in incidence of ovarian cancer was detected for individuals with the highest quintile of kaempferol consumption compared to those in the lowest quintile. [106],[125] The intake of this nontoxic and inexpensive phytochemical can be easily adopted into the lifestyle of most women. [126]

Metabolic sites reveal large fluctuations toward flavonoid cytotoxicity

Present in dietary sources mostly as glycosides, flavonoids are cleaved in intestine by microbial enzymes and further metabolized in colon and liver to release into the blood as different conjugates. In this way, the epithelium of intestine is exposed to higher concentrations of flavonoids and their different metabolites than the tissues at other locations; and this would also be true for the colonic tumor cells, showing that colorectal cancer appears most relevant to dietary factors. [45],[127] At the same time, the exposure to different metabolites can explain the large fluctuations in cytotoxic constants of flavonoids measured using colorectal and liver cancer cell lines. It is possible that some metabolites could be more cytotoxic than parent compounds, giving a selective anticancer activity advantage in vivo.

The other aspect important to take into consideration by analyzing the cytotoxic data of flavonoids includes their differential effect against tumors with specific mutational spectra. The differential effectiveness of inhibition of cell growth and arresting cell cycle in response to flavonoids in various colorectal cancer cell lines may be associated with the functional status of p53 and/or ras genes. While apigenin has been indicated to have stronger effect on tumors with mutations in genes which are critical to colon cancer development, thus being more effective in controlling the growth of tumors with certain mutational spectra and less effective in wild-type normal cells, [29],[46],[127] kaempferol and hesperetin seem to exhibit higher resistance toward mutant p53 human colon cancer cell lines. [125],[128]

Some other flavonoids including quercetin and baicalein have also been shown to be useful agents for prevention and treatment of colon cancer [Table 2]. However, compared to quercetin and baicalein, their glycosides rutin and baicalin, respectively showed no growth inhibitory effects on colon cancer cells, [20],[129] showing that the sugar moiety strongly affects the bioactivity of flavonoids.

Accumulated evidences have indicated that the growth of hepatocarcinoma cells can be suppressed by flavones apigenin, luteolin, wogonin, and baicalin, thus being valuable for the therapeutic intervention of human hepatomas [Table 2]. Apigenin may have some implications also in the prevention of virus infection, leading to liver cancer development; [130] wogonin possesses hepatoprotective activities against diverse pathophysiological processes associated with hepatocarcinogenesis and can be extremely competitive as anticancer drugs against malignant hepatoma. [131],[132]

Blood cells are potent target sites for flavonoids

Anticancer drugs are generally more effective against leukemia than other malignancies and in this aspect flavonoids are similar to other anticancer agents. [24] The mean cytotoxic constants of various flavonoids on different blood cancer cells are depicted in the [Figure 2] showing that many common dietary polyphenols exhibit growth inhibitory properties against several human hematologic malignancies.
Figure 2: Cytotoxic effect of flavonoids on different human blood cancer cell lines

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Flavonoids hold much promise for the development of new chemotherapeutics in myeloid and lymphoid leukemias. [133],[134],[135] In general, flavonol aglycones (quercetin, kaempferol, myricetin) seem to exhibit somewhat stronger cytotoxic activity against blood cancer cells of myeloid lineage compared to lymphocytic leukemia cell lines, whereas flavonol glycosides have no effect on the viability of different blood cancer cells. In contrast to the inactivity of flavanone naringenin in myeloid and lymphoid leukemia cell lines, this dietary polyphenol exerts cytotoxicity on erythroleukemia cells, thus revealing an opposite situation to flavones (apigenin, luteolin, tangeretin) in which cases strong anticancer activity has been measured in cell lines of myeloid and lymphoid lineages but significantly lower sensitivity is expressed toward erythroleukemia cells [Figure 2]. This knowledge could be specifically applied in chemoprevention as well as clinical trials for treatment of different hematologic malignancies.

Polyphenols affecting both hormone-dependent and -independent tumor cells

Breast and prostate cancers are hormone-dependent tumors as their development and growth can be dependent on the expression of estrogen receptors (ER) and androgen receptors (AR), respectively.

Most breast cancers are heterogeneous and consist of ER-positive and -negative cells. Therefore, agents that are able to inhibit the growth of both ER-positive and -negative tumors are of great interest. [136] Dietary flavonoids seem to display such dual activity, inhibiting both receptor-positive and -negative breast cancer cells [Table 2]. For instance, no difference in the cytotoxicity of naringenin has been found between human breast cancer cell lines expressing or not expressing ERs [24] and the regular intake of this flavanone may slow down the rate at which breast cancer cells proliferate. [103] High flavone intake has also been significantly correlated with a lower risk of breast cancer [68] and apigenin, baicalein, and luteolin may be promising candidate agents in the treatment of mammary tumors. [137],[138],[139] However, although apigenin can target both ER-dependent and -independent pathways, it seems to be somewhat more potent on ER-positive human breast cancer cell lines [Figure 3], thus providing more promise for the treatment of ER-positive tumors.
Figure 3: Cytotoxic effect of apigenin on human breast cancer cell lines depending on the expression of estrogen receptors

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AR are the critical factors for the prostate cancer cell growth and survival and in the development of ablation-resistant prostate tumors. As presented in [Table 2], flavonoids display anticancer effects both in AR-positive and -negative prostate cancer cell lines. However, flavonol aglycones (quercetin, fisetin, galangin, kaempferol, and myricetin) exert somewhat stronger cytotoxic activity on AR-dependent prostate cancer cells [Figure 4]. Indeed, quercetin has been shown to decrease the androgen receptor expression in 22rv1 human prostate cancer cells, [140] whereas fisetin can inhibit the AR signaling pathways [141],[142] showing that these compounds may afford more health benefits in chemoprevention and earlier stages of prostate carcinogenesis when the tumor is still dependent on the presence of androgens. In contrast, flavanone naringenin seem to display only very low potency toward AR-positive human prostate cancer cells, suppressing at the same time the growth of androgen-independent human prostate cancer lines. Flavones like apigenin, baicalein, and baicalin express rather similar pattern of growth inhibition of both AR-positive and -negative prostate carcinoma cells, thus being independent on androgen receptor status. [66],[143],[144] Flavonoid treatment may offer an alternative strategy to suppress androgen-insensitive prostate tumor growth and flavonoids like naringenin, apigenin, baicalein, chrysin, and luteolin may be developed as promising chemotherapeutic agents against advanced and androgen-independent human prostate tumors.
Figure 4: Cytotoxic effect of flavonols on human prostate cancer cell lines depending on the expression of androgen receptors

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Table 1: Structures and main food sources of major flavonoid aglycones and their glycosides

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With regards to the structure of flavonoids and nature of substituents, it is especially important to point out the fact that methylation of the hydroxyl groups does not reduce the anticancer capacity but even increases it. [61],[69] Therefore, polymethoxylated flavonoids, such as tangeretin and nobiletin, can be much more potent inhibitors of tumor cell growth than free hydroxylated flavonoids [69],[145] [Table 2].
Table 2: Cytotoxicity of flavonoids on human cancer cell lines derived from various organ sites (mean IC50±SE, μM (n)). Cell lines used for assays are presented in Table 3

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Table 3: Human cancer cell lines used for cytotoxicity assays of flavonoids

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Lung and uterine cancer as well as melanoma cells are strongly affected by flavonoids

Cytotoxic effects of flavonoids on malignant cell lines derived from human lung and cervical cancers as well as melanoma are depicted in [Figure 5]. Several flavonol aglycones are able to cause decrease in cell viability with half-maximal cytotoxic doses in low micromolar range [Table 2], revealing the most potent cytotoxic activity for myricetin in lung cancer cells and quercetin in melanoma and cervical cancer cells. Flavanones display no growth inhibitory effect on lung and cervical cancer cell lines, expressing at the same time some cytotoxicity on human melanoma cells.
Figure 5: Cytotoxic effect of flavonoids on different human lung cancer cell lines (a), melanoma cell lines (b), and uterine cancer cell lines (c)

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Several members of the flavone group display high cytotoxic activity against cervical cancer cells. Apigenin is probably more potent and sensitive in killing cervical cancer cells than cells of melanoma and lung cancer; the same seems to be true also for chrysin. Luteolin exerts high-level activity both in cervical cancer as well as melanoma cell lines, showing that these flavones may have good perspectives as lead compounds of potent antitumor agents for the respective target sites. On the other hand, polymethoxylated flavones nobiletin and tangeretin are among the most effective at inhibiting cancer cell growth of melanoma and lung (tangeretin) and it is also the reason why these dietary polyphenols have emerged as potential drug candidates for treatment of these malignancies [Table 2], [Figure 5].

   Conclusions and further perspectives Top

Flavonoids can play important beneficial roles in human nutrition and health status and chemoprevention is one of the most realistic and promising approaches for the prevention of malignant disorders. [76],[118] Diet-health relationships are very complex as food items usually act through multiple pathways and each ingredient can have different molecular targets. It is also the reason why phytochemical combinations may offer greater chemoprevention than administration of single agents alone. [110] Both additive as well as synergistic interactions between several dietary flavonoids have been reported, [101],[146] contributing to the health benefits of fruits and vegetables. Therefore, consumers may gain more significant health benefits from whole foods than from intake of dietary supplements. [146] However, individual phenolic compounds may also act antagonistically with other components, [147],[148] and further efforts are necessary to understand their action modes as well as to provide further information for the cancer prevention in future. [149]

Flavonoids are not only promising food-derived cancer preventive compounds but could also be considered as candidates for chemotherapeutic agents, revealing potential clinical significance in the cancer treatment. [73],[150] Polyphenolic compounds like quercetin, myricetin, apigenin, baicalein, chrysin, luteolin, nobiletin, and tangeretin might be valuable agents in anticancer strategies and studies of their clinical use for development of novel drugs should be continued. Beneficial effects have been described also by combining certain flavonoids with standard chemotherapeutic drugs leading to decrease in the dosage and associated toxicity while targeting specific resistance mechanisms. In this way, the genotoxic damage caused by standard chemotherapeutics to normal cells can be diminished, thereby reducing the chance of developing of secondary cancers. [45],[151] Further work is certainly needed to develop and produce novel drugs from natural sources introducing structural variations into the backbone of flavonoids and modifying their structures to further improve biological activity and exhibit more potent anticancer effects.[326]

Despite a rather short period of investigation of the anticancer action of flavonoids (for instance, apigenin was first proposed to interfere with the process of carcinogenesis only in 1980s), [45] this field has undergone an extensive development. The cytotoxic data of flavonoids compiled within the current work and relationships presented in this review article cannot only be useful in chemoprevention to choose the food items containing most active natural polyphenols on malignant cells of certain cancer types, considering the individual genetic cancer risks and familial anamnesis but also in the selection of parent compounds to design and synthesize novel chemotherapy drugs starting from the valuable material given to us by the nature.

   References Top

1.Mignet N, Seguin J, Ramos Romano M, Brulle L, Touil YS, Scherman D, et al. Development of a liposomal formulation of the natural flavonoid fisetin. Int J Pharm 2012;423:69-76.  Back to cited text no. 1
2.Ying TH, Yang SF, Tsai SJ, Hsieh SC, Huang YC, Bau DT, et al. Fisetin induces apoptosis in human cervical cancer HeLa cells through ERK1/2-mediated activation of caspase-8-/caspase-3-dependent pathway. Arch Toxicol 2012;86:263-73.  Back to cited text no. 2
3.Szliszka E, Helewski KJ, Mizgala E, Krol W. The dietary flavonol fisetin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells. Int J Oncol 2011;39:771-9.  Back to cited text no. 3
4.Seguin J, Brullé L, Boyer R, Lu YM, Ramos Romano M, Touil YS, et al. Liposomal encapsulation of the natural flavonoid fisetin improves bioavailability and antitumor efficacy. Int J Pharm 2013;444:146-54.  Back to cited text no. 4
5.Tolomeo M, Grimaudo S, Di Cristina A, Pipitone RM, Dusonchet L, Meli M, et al. Galangin increases the cytotoxic activity of imatinib mesylate in imatinib-sensitive and imatinib-resistant Bcr-Abl expressing leukemia cells. Cancer Lett 2008;265:289-97.  Back to cited text no. 5
6.Jaiswal JV, Wadegaonkar PA, Hajare SW. The bioflavonoid galangin suppresses the growth of ehrlich ascites carcinoma in Swiss Albino mice: A molecular insight. Appl Biochem Biotechnol 2012;167:1325-39.  Back to cited text no. 6
7.Zhang HT, Luo H, Wu J, Lan LB, Fan DH, Zhu KD, et al. Galangin induces apoptosis of hepatocellular carcinoma cells via the mitochondrial pathway. World J Gastroenterol 2010;16:3377-84.  Back to cited text no. 7
8.Hsiao YC, Hsieh YS, Kuo WH, Chiou HL, Yang SF, Chiang WL, et al. The tumor-growth inhibitory activity of flavanone and 2`-OH flavanone in vitro and in vivo through induction of cell cycle arrest and suppression of cyclins and CDKs. J Biomed Sci 2007;14:107-19.  Back to cited text no. 8
9.Ou YC, Kuan YH, Li JR, Raung SL, Wang CC, Hung YY, et al. Induction of apoptosis by luteolin involving akt inactivation in human 786-o renal cell carcinoma cells. Evid Based Complement Alternat Med 2013;2013:109105.  Back to cited text no. 9
10.Shen SC, Ko CH, Tseng SW, Tsai SH, Chen YC. Structurally related antitumor effects of flavanones in vitro and in vivo: Involvement of caspase 3 activtion, p21 gene expression, and reactive oxygen species production. Toxicol Appl Pharmacol 2004;197:84-95.  Back to cited text no. 10
11.Ramesh E, Alshatwi AA. Naringin induces death receptor and mitochondria-mediated apoptosis in human cervical cancer (SiHa) cells. Food Chem Toxicol 2013;51:97-105.  Back to cited text no. 11
12.Zhao X, Shu G, Chen L, Mi X, Mei Z, Deng X. A flavonoid component from Docynia Delavayi (Franch.) Schneid represses transplanted H22 hepatoma growth and exhibits low toxic effect on tumor-bearing mice. Food Chem Toxicol 2012;50:3166-73.  Back to cited text no. 12
13.Kim JH, Jung CH, Jang BH, Go HY, Park JH, Choi YK, et al. Selective cytotoxic effects on human cancer cell lines of phenolic-rich ethyl-acetate fraction from Rhus verniciflua Stokes. Am J Chin Med 2009;37:609-20.  Back to cited text no. 13
14.Li YL, Gan GP, Zhang HZ, Wu HZ, Li CL, Huang YP, et al. A flavonoid glycoside isolated from Smilax china L. rhizome in vitro anticancer effects on human cancer cell lines. J Ethnopharmacol 2007;113:115-24.  Back to cited text no. 14
15.Attoub S, Hassan AH, Vanhoecke B, Iratni R, Takahashi T, Gaben AM, et al. Inhibition of cell survival, invasion, tumor growth and histone deacetylase activity by the dietary flavonoid luteolin in human epithelioid cancer cells. Eur J Pharmacol 2011;651:18-25.  Back to cited text no. 15
16.Li-Weber M. New therapeutic aspects of flavones: The anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat Rev 2009;35:57-68.  Back to cited text no. 16
17.Samarghandian S, Afshari JT, Davoodi S. Chrysin reduces proliferation and induces apoptosis in the human prostate cancer cell line pc-3. Clinics (Sao Paulo) 2011;66:1073-9.  Back to cited text no. 17
18.Tundis R, Loizzo MR, Menichini F, Bonesi M, Colica C, Menichini F. In vitro cytotoxic activity of extracts and isolated constituents of Salvia leriifolia Benth. against a panel of human cancer cell lines. Chem Biodivers 2011;8:1152-62.  Back to cited text no. 18
19.Kalim MD, Bhattacharyya D, Banerjee A, Chattopadhyay S. Oxidative DNA damage preventive activity and antioxidant potential of plants used in Unani system of medicine. BMC Complement Altern Med 2010;10:77.  Back to cited text no. 19
20.Wang CZ, Calway TD, Wen XD, Smith J, Yu C, Wang Y, et al. Hydrophobic flavonoids from Scutellaria baicalensis induce colorectal cancer cell apoptosis through a mitochondrial-mediated pathway. Int J Oncol 2013;42:1018-26.  Back to cited text no. 20
21.Abrahim NN, Kanthimathi MS, Abdul-Aziz A. Piper betle shows antioxidant activities, inhibits MCF-7 cell proliferation and increases activities of catalase and superoxide dismutase. BMC Complement Altern Med 2012;12:220.  Back to cited text no. 21
22.Hamedeyazdan S, Fathiazad F, Sharifi S, Nazemiyeh H. Antiproliferative activity of Marrubium persicum extract in the MCF-7 human breast cancer cell line. Asian Pac J Cancer Prev 2012;13:5843-8.  Back to cited text no. 22
23.Suttana W, Mankhetkorn S, Poompimon W, Palagani A, Zhokhov S, Gerlo S, et al. Differential chemosensitization of P-glycoprotein overexpressing K562/Adr cells by withaferin A and Siamois polyphenols. Mol Cancer 2010;9:99.  Back to cited text no. 23
24.Kanno S, Tomizawa A, Hiura T, Osanai Y, Shouji A, Ujibe M, et al. Inhibitory effects of naringenin on tumor growth in human cancer cell lines and sarcoma S-180-implanted mice. Biol Pharm Bull 2005;28:527-30.  Back to cited text no. 24
25.Bestwick CS, Milne L. Influence of galangin on HL-60 cell proliferation and survival. Cancer Lett 2006;243:80-9.  Back to cited text no. 25
26.Morales P, Haza AI. Selective apoptotic effects of piceatannol and myricetin in human cancer cells. J Appl Toxicol 2012;32:986-93.  Back to cited text no. 26
27.Chien CS, Shen KH, Huang JS, Ko SC, Shih YW. Antimetastatic potential of fisetin involves inactivation of the PI3K/Akt and JNK signaling pathways with downregulation of MMP-2/9 expressions in prostate cancer PC-3 cells. Mol Cell Biochem 2010;333:169-80.  Back to cited text no. 27
28.Sato F, Matsukawa Y, Matsumoto K, Nishino H, Sakai T. Apigenin induces morphological differentiation and G2-M arrest in rat neuronal cells. Biochem Biophys Res Commun 1994;204:578-84.  Back to cited text no. 28
29.Chung CS, Jiang Y, Cheng D, Birt DF. Impact of adenomatous polyposis coli (APC) tumor supressor gene in human colon cancer cell lines on cell cycle arrest by apigenin. Mol Carcinog 2007;46:773-82.  Back to cited text no. 29
30.Kilani-Jaziri S, Frachet V, Bhouri W, Ghedira K, Chekir-Ghedira L, Ronot X. Flavones inhibit the proliferation of human tumor cancer cell lines by inducing apoptosis. Drug Chem Toxicol 2012;35:1-10.  Back to cited text no. 30
31.Lee EJ, Oh SY, Sung MK. Luteolin exerts anti-tumor activity through the suppression of epidermal growth factor receptor-mediated pathway in MDA-MB-231 ER-negative breast cancer cells. Food Chem Toxicol 2012;50:4136-43.  Back to cited text no. 31
32.Bulzomi P, Bolli A, Galluzzo P, Acconcia F, Ascenzi P, Marino M. The naringenin-induced proapoptotic effect in breast cancer cell lines holds out against a high nisphenol a background. IUBMB Life 2012;64:690-6.  Back to cited text no. 32
33.Dai Z, Nair V, Khan M, Ciolino HP. Pomegranate extract inhibits the proliferation and viability of MMTV-Wnt-1 mouse mammary cancer stem cells in vitro. Oncol Rep 2010;24:1087-91.  Back to cited text no. 33
34.Morley KL, Ferguson PJ, Koropatnick J. Tangeretin and nobiletin induce G1 cell cycle arrest but not apoptosis in human breast and colon cancer cells. Cancer Lett 2007;251:168-78.  Back to cited text no. 34
35.Yin F, Giuliano AE, Law RE, Van Herle AJ. Apigenin inhibits growth and induces G2/M arrest by modulating cyclin-CDK regulators and ERK MAP kinase activation in breast carcinoma cells. Anticancer Res 2001;21:413-20.  Back to cited text no. 35
36.Takagaki N, Sowa Y, Oki T, Nakanishi R, Yogosawa S, Sakai T. Apigenin induces cell cycle arrest and p21/WAF1 expression in a p53-independent pathway. Int J Oncol 2005;26:185-9.  Back to cited text no. 36
37.Pacifico S, Scognamiglio M, D`Abrosca B, Piccolella S, Tsafantakis N, Gallicchio M, et al. Spectroscopic characterization and antiproliferative activity on HepG2 human hepatoblastoma cells of flavonoid C-glycosides from Petrorhagia velutina. J Nat Prod 2010;73:1973-8.  Back to cited text no. 37
38.Jeong JC, Kim MS, Kim TH, Kim YK. Kaempferol induces cell death through ERK and Akt-dependent down-regulation of XIAP and survivin in human glioma cells. Neurochem Res 2009;34:991-1001.  Back to cited text no. 38
39.Kim DA, Jeon YK, Nam MJ. Galangin Induces apoptosis in gastric cancer cells via regulation of ubiquitin carboxy-terminal hydrolase isozyme L1 and glutathione S-transferase P. Food Chem Toxicol 2012;50:684-8.  Back to cited text no. 39
40.Amado NG, Cerqueira DM, Menezes FS, da Silva JF, Neto VM, Abreu JG. Isoquercitrin isolated from Hyptis fasciculata reduces glioblastoma cell proliferation and changes beta-catenin cellular localization. Anticancer Drugs 2009;20:543-52.  Back to cited text no. 40
41.Lee ER, Kang YJ, Choi HY, Kang GH, Kim JH, Kim BW, et al. Induction of apoptotic cell death by synthetic naringenin derivatives in human lung epithelial carcinoma A549 cells. Biol Pharm Bull 2007;30:2394-8.  Back to cited text no. 41
42.Shih YW, Wu PF, Lee YC, Shi MD, Chiang TA. Myricetin suppresses invasion and migration of human lung adenocarcinoma A549 cells: Possible mediation by blocking the ERK signaling pathway. J Agric Food Chem 2009;57:3490-9.  Back to cited text no. 42
43.Ninomiya M, Nishida K, Tanaka K, Watanabe K, Koketsu M. Structure-activity relationship studies of 5,7-dihydroxyflavones as naturally occurring inhibitors of cell proliferation in human leukemia HL-60 cells. J Nat Med 2013;67:460-7.  Back to cited text no. 43
44.Wang BD, Yang ZY, Wang Q, Cai TK, Crewdson P. Synthesis, characterization, cytotoxic activities, and DNA-binding properties of the La(III) complex with Naringenin Schiff-base. Bioorg Med Chem 2006;14:1880-8.  Back to cited text no. 44
45.Lefort EC, Blay J. Apigenin and its impact on gastrointestinal cancers. Mol Nutr Food Res 2013;57:126-44.  Back to cited text no. 45
46.Wang W, VanAlstyne PC, Irons KA, Chen S, Stewart JW, Birt DF. Individual and interactive effects of apigenin analogs on G2/M cell-cycle arrest in human colon carcinoma cell lines. Nutr Cancer 2004;48:106-14.  Back to cited text no. 46
47.Patel D, Shukla S, Gupta S. Apigenin and cancer chemoprevention: Progress, potential and promise (review). Int J Oncol 2007;30:233-45.  Back to cited text no. 47
48.Khoo BY, Chua SL, Balaram P. Apoptotic effects of chrysin in human cancer cell lines. Int J Mol Sci 2010;11:2188-99.  Back to cited text no. 48
49.Li N, Liu JH, Zhang J, Yu BY. Comparative evaluation of cytotoxicity and antioxidative activity of 20 flavonoids. J Agric Food Chem 2008;56:3876-83.  Back to cited text no. 49
50.Guthrie N, Carroll KK. Inhibition of mammary cancer by citrus flavonoids. Adv Exp Med Biol 1998;439:227-36.  Back to cited text no. 50
51.Knowles LM, Zigrossi DA, Tauber RA, Hightower C, Milner JA. Flavonoids suppress androgen-independent human prostate tumor proliferation. Nutr Cancer 2000;38:116-22.  Back to cited text no. 51
52.Torkin R, Lavoie JF, Kaplan DR, Yeger H. Induction of caspase-dependent, p53-mediated apoptosis by apigenin in human neuroblastoma. Mol Cancer Ther 2005;4:1-11.  Back to cited text no. 52
53.Yoshimizu N, Otani Y, Saikawa Y, Kubota T, Yoshida M, Furukawa T, et al. Anti-tumour effects of nobiletin, a citrus flavonoid, on gastric cancer include: Antiproliferative effects, induction of apoptosis and cell cycle deregulation. Aliment Pharmacol Ther 2004;20:95-101.  Back to cited text no. 53
54.Fotsis T, Pepper MS, Aktas E, Breit S, Rasku S, Adlercreutz H, et al. Flavonoids, dietary-derived inhibitors of cell proliferation and in vitro angiogenesis. Cancer Res 1997;57:2916-21.  Back to cited text no. 54
55.Fotsis T, Pepper MS, Montesano R, Aktas E, Breit S, Schweigerer L, et al. Phytoestrogens and inhibition of angiogenesis. Baillieres Clin Endocrinol Metab 1998;12:649-66.  Back to cited text no. 55
56.Lim do Y, Jeong Y, Tyner AL, Park JH. Induction of cell cycle arrest and apoptosis in HT-29 human colon cancer cells by the dietary compound luteolin. Am J Physiol Gastrointest Liver Physiol 2007;292:G66-75.  Back to cited text no. 56
57.Gupta S, Afaq F, Mukhtar H. Selective growth-inhibitory, cell-cycle deregulatory and apoptotic response of apigenin in normal versus human prostate carcinoma cells. Biochem Biophys Res Commun 2001;287:914-20.  Back to cited text no. 57
58.Yuan E, Liu B, Ning Z, Chen C. Preparative separation of flavonoids in Adinandra nitida leaves by high-speed counter-current chromatography and their effects on human epidermal carcinoma cancer cells. Food Chem 2009;115:1158-63.  Back to cited text no. 58
59.Tokalov SV, Abramyuk AM, Abolmaali ND. Protection of p53 wild type cells from taxol by genistein in the combined treatment of lung cancer. Nutr Cancer 2010;62:795-801.  Back to cited text no. 59
60.Plochmann K, Korte G, Koutsilieri E, Richling E, Riederer P, Rethwilm A, et al. Structure-activity relationships of flavonoid-induced cytotoxicity on human leukemia cells. Arch Biochem Biophys 2007;460:1-9.  Back to cited text no. 60
61.Ben Sghaier M, Skandrani I, Nasr N, Franca MG, Chekir-Ghedira L, Ghedira K. Flavonoids and sesquiterpenes from Tecurium ramosissimum promote antiproliferation of human cancer cells and enhance antioxidant activity: A structure-activity relationship study. Environ Toxicol Pharmacol 2011;32:336-48.  Back to cited text no. 61
62.Hirano T, Abe K, Gotoh M, Oka K. Citrus flavone tangeretin inhibits leukaemic HL-60 cell growth partially through induction of apoptosis with less cytotoxicity on normal lymphocytes. Br J Cancer 1995;72:1380-8.  Back to cited text no. 62
63.Chiu FL, Lin JK. Downregulation of androgen receptor expression by luteolin causes inhibition of cell proliferation and induction of apoptosis in human prostate cancer cells and xenografts. Prostate 2008;68:61-71.  Back to cited text no. 63
64.Galvez M, Martin-Cordero C, Lopez-Lazaro M, Cortes F, Ayuso MJ. Cytotoxic effect of Plantago spp. on cancer cell lines. J Ethnopharmacol 2003;88:125-30.  Back to cited text no. 64
65.Choi EJ. Hesperetin induced G1-phase cell cycle arrest in human breast cancer MCF-7 cells: Involvement of CDK4 and p21. Nutr Cancer 2007;59:115-9.  Back to cited text no. 65
66.Chan FL, Choi HL, Chen ZY, Chan PS, Huang Y. Induction of apoptosis in prostate cancer cell lines by a flavonoid, baicalin. Cancer Lett 2000;160:219-28.  Back to cited text no. 66
67.Androutsopoulos VP, Ruparelia K, Arroo RR, Tsatsakis AM, Spandidos DA. CYP1-mediated antiproliferative activity of dietary flavonoids in MDA-MB-468 breast cancer cells. Toxicology 2009;264:162-70.  Back to cited text no. 67
68.Seelinger G, Merfort I, Wölfle U, Schempp CM. Anti-carcinogenic effects of the flavonoid luteolin. Molecules 2008;13:2628-51.  Back to cited text no. 68
69.Benavente-Garcia O, Castillo J. Update on uses and properties of citrus flavonoids: New findings in anticancer, cardiovascular, and anti-inflammatory activity. J Agric Food Chem 2008;56:6185-205.  Back to cited text no. 69
70.Wätjen W, Weber N, Lou YJ, Wang ZQ, Chovolou Y, Kampkötter A, et al. Prenylation enhances cytotoxicity of apigenin and liquiritigenin in rat H4IIE hepatoma and C6 glioma cells. Food Chem Toxicol 2007;45:119-24.  Back to cited text no. 70
71.Cai X, Ye T, Liu C, Lu W, Lu M, Zhang J, et al. Luteolin induced G2 phase cell cycle arrest and apoptosis on non-small cell lung cancer cells. Toxicol In Vitro 2011;25:1385-91.  Back to cited text no. 71
72.Zhang Y, Chen AY, Li M, Chen C, Yao Q. Ginkgo biloba extract kaempferol inhibits cell proliferation and induces apoptosis in pancreatic cancer cells. J Surg Res 2008;148:17-23.  Back to cited text no. 72
73.Xu XF, Cai BL, Guan SM, Li Y, Wu JZ, Wang Y, et al. Baicalin induces human mucoepidermoid carcinoma Mc3 cells apoptosis in vitro and in vivo. Invest New Drugs 2011;29:637-45.  Back to cited text no. 73
74.Lee WR, Shen SC, Lin HY, Hou WC, Yang LL, Chen YC. Wogonin and fisetin induce apoptosis in human promyeloleukemic cells, accompanied by a decrease of reactive oxygen species, and activation of caspase 3 and Ca(2+)-dependent endonuclease. Biochem Pharmacol 2002;63:225-36.  Back to cited text no. 74
75.Park JH, Jin CY, Lee BK, Kim GY, Choi YH, Jeong YK. Naringenin induces apoptosis through downregulation of Akt and caspase-3 activation in human leukemia THP-1 cells. Food Chem Toxicol 2008;46:3684-90.  Back to cited text no. 75
76.Anter J, Romero-Jimenez M, Fernandez-Badmar Z, Villatoro-Pulido M, Analla M, Alonso-Moraga A, et al0. Antigenotoxicity, cytotoxicity, and apoptosis induction by apigenin, bisabolol, and protocatechuic acid. J Med Food 2011;14:276-83.  Back to cited text no. 76
77.Choi EJ, Kim GH. Apigenin causes G(2)/M arrest associated with the modulation of p21(Cip1) and Cdc2 and activates p53-dependent apoptosis pathway in human breast cancer SK-BR-3 cells. J Nutr Biochem 2009;20:285-90.  Back to cited text no. 77
78.Kajimoto S, Takanashi N, Kajimoto T, Xu M, Cao J, Masuda Y, et al. Sophoranone, extracted from a traditional Chinese medicine Shan Dou Gen, induces apoptosis in human leukemia U937 cells via formation of reactive oxygen species and opening of mitochondrial permeability transition pores. Int J Cancer 2002;99:879-90.  Back to cited text no. 78
79.Lin CC, Kuo CL, Lee MH, Lai KC, Lin JP, Yang JS, et al. Wogonin triggers apoptosis in human osteosarcoma U-2 OS cells through the endoplasmic reticulum stress, mitochondrial dysfunction and caspase-3-dependent signaling pathways. Int J Oncol 2011;39:217-24.  Back to cited text no. 79
80.Fu J, Chen D, Zhao B, Zhao Z, Zhou J, Xu J, et al. Luteolin induces carcinoma cell apoptosis through binding Hsp90 to suppress constitutive activation of STAT3. PloS One 2012;e49194.  Back to cited text no. 80
81.Jeong JH, An JY, Kwon YT, Rhee JG, Lee YJ. Effects of low dose quercetin: Cancer cell-specific inhibition of cell cycle progression. J Cell Biochem 2009;106:73-82.  Back to cited text no. 81
82.Lu X, Jung Ji, Cho HJ, Lim DY, Lee HS, Chun HS, et al. Fisetin inhibits the activities of cyclin-dependent kinases leading to cell cycle arrest in HT-29 human colon cancer cells. J Nutr 2005;135:2884-90.  Back to cited text no. 82
83.Shukla S, Gupta S. Apigenin-induced cell cycle arrest is mediated by modulation of MAPK, PI3K-Akt, and loss of cyclin D1 associated retinoblastoma dephosphorylation in human prostate cancer cells. Cell Cycle 2007;6:1102-14.  Back to cited text no. 83
84.Koide T, Kamei H, Hashimoto Y, Kojima T, Terabe K, Umeda T. Influence of flavonoids on cell cycle phase as analyzed by flow-cytometry. Cancer Biother Radiopharm 1997;12:111-5.  Back to cited text no. 84
85.Neves MP, Cidade H, Pinto M, Silva AM, Gales L, Damas AM, et al. Prenylated derivatives of baicalein and 3,7-dihydroxyflavone: Synthesis and study of their effects on tumor cell lines growth, cell cycle and apoptosis. Eur J Med Chem 2011;46:2562-74.  Back to cited text no. 85
86.Leung HW, Lin CJ, Hour MJ, Yang WH, Wang MY, Lee HZ. Kaempferol induces apoptosis in human lung non-small carcinoma cells accompanied by an induction of antioxidant enzymes. Food Chem Toxicol 2007;45:2005-13.  Back to cited text no. 86
87.Habtemarium S, Dagne E. Comparative antioxidant, prooxidant and cytotoxic activity of sigmoidin A and eriodictyol. Planta Med 2010;76:589-94.  Back to cited text no. 87
88.Valdameri G, Trombetta-Lima M, Worfel PR, Pires AR, Martinez GR, Noleto GR, et al. Involvement of catalase in the apoptotic mechanism induced by apigenin in HepG2 human hepatoma cells. Chem Biol Interact 2011;193:180-9.  Back to cited text no. 88
89.Yuan L, Wang J, Xiao H, Xiao C, Wang Y, Liu X. Isoorientin induces apoptosis through mitochondrial dysfunction and inhibition of PI3K/Akt signaling pathway in HepG2 cancer cells. Toxicol Appl Pharmacol 2012;265:83-92.  Back to cited text no. 89
90.Xu Y, Xin Y, Diao Y, Lu C, Fu J, Luo L, et al. Synergistic effects of apigenin and paclitaxel on apoptosis of cancer cells. PLoS One 2011;6:e29169.  Back to cited text no. 90
91.Tsai CF, Yeh WL, Huang SM, Tan TW, Lu DY. Wogonin induces reactive oxygen species production and cell apoptosis in human glioma cancer cells. Int J Mol Sci 2012;13:9877-92.  Back to cited text no. 91
92.Matsuo M, Sasaki N, Saga K, Kaneko T. Cytotoxicity of flavonoids toward cultured normal human cells. Biol Pharm Bull 2005;28:253-9.  Back to cited text no. 92
93.Agullo G, Gamet-Payrastre L, Fernandez Y, Anciaux N, Demigne C, Rémésy C. Comparative effects of flavonoids on the growth, viability and metabolism of a colonic adenocarcinoma cell line (HT29 cells). Cancer Lett 1996;105:61-70.  Back to cited text no. 93
94.Lee KW, Hur HJ, Lee HJ, Lee CY. Antiproliferative effects of dietary phenolic substances and hydrogen peroxide. J Agric Food Chem 2005;53:1990-5.  Back to cited text no. 94
95.Talib WH, Zarga MH, Mahasneh AM. Antiproliferative, antimicrobial and apoptosis inducing effects of compounds isolated from inula viscosa. Molecules 2012;17:3291-303.  Back to cited text no. 95
96.Benavente-Garcia O, Castillo J, Lorente J, Alcaraz M, Yanez J, Martinez C, et al. Antiproliferative activity of several phenolic compounds against melanoma cell lines: Relationship between structure and activity. Agro Food Ind Hi-Tech 2005;16:30-4.  Back to cited text no. 96
97.Rodriguez J, Yanez J, Vicente V, Alcaraz M, Benavente-Garcia O, Castillo J, et al. Effects of several flavonoids on the growth of B16F10 and SK-MEL-1 melanoma cell lines: Relationship between structure and activity. Melanoma Res 2002;12:99-107.  Back to cited text no. 97
98.Ragazzon PA, Bradshaw T, Matthews C, Iley J, Missailidis S. The characterisation of flavone-DNA isoform interactions as a basis for anticancer drug development. Anticancer Res 2009;29:2273-83.  Back to cited text no. 98
99.Mamadalieva NZ, Herrmann F, El-Readi MZ, Tahrani A, Hamoud R, Egamberdieva DR, et al. Flavonoids in Scutellaria immaculata and S. ramosissima (Lamiaceae) and their biological activity. J Pharm Pharmacol 2011;63:1346-57.  Back to cited text no. 99
100.Rao PS, Satelli A, Moridani M, Jenkins M, Rao US. Luteolin induces apoptosis in multidrug resistant cancer cells without affecting the drug transporter function: Involvement of cell line-specific apoptotic mechanisms. Int J Cancer 2012;130:2703-14.  Back to cited text no. 100
101.Androutsopoulos VP, Spandidos DA. The flavonoids diosmetin and luteolin exert synergistic cytostatic effects in human hepatoma HepG2 cells via CYP1A-catalyzed metabolism, activation of JNK and ERK and P53/P21 up-regulation. J Nutr Biochem 2013;24:496-504.  Back to cited text no. 101
102.Jin CY, Park C, Lee JH, Chung KT, Kwon TK, Kim GY, et al. Naringenin-induced apoptosis is attenuated by Bcl-2 but restored by the small molecule Bcl-2 inhibitor, HA 14-1, in human leukemia U937 cells. Toxicol In Vitro 2009;23:259-65.  Back to cited text no. 102
103.Harmon AW, Patel YM. Naringenin inhibits glucose uptake in MCF-7 breast cancer cells: A mechanism for impaired cellular proliferation. Breast Cancer Res Treat 2004;85:103-10.  Back to cited text no. 103
104.Yang Y, Wolfram J, Boom K, Fang X, Shen H, Ferrari M. Hesperetin impairs glucose uptake and inhibits proliferation of breast cancer cells. Cell Biochem Funct 2013;31:374-9.  Back to cited text no. 104
105.Pandey M, Kaur P, Shukla S, Abbas A, Fu P, Gupta S. Plant flavone apigenin inhibits HDAC and remodels chromatin to induce growth arrest and apoptosis in human prostate cancer cells: In vitro and in vivo study. Mol Carcinog 2012;51:952-62.  Back to cited text no. 105
106.Luo H, Jiang B, Li B, Li Z, Jiang BH, Chen YC. Kaempferol nanoparticles achieve strong and selective inhibition of ovarian cancer cell viability. Int J Nanomedicine 2012;7:3951-9.  Back to cited text no. 106
107.Xiao H, Yang CS, Li S, Jin H, Ho CT, Patel T. Monodemethylated polymethoxyflavones from sweet orange (Citrus sinensis) peel inhibit growth of human lung cancer cells by apoptosis. Mol Nutr Food Res 2009;53:398-406.  Back to cited text no. 107
108.Walle T, Ta N, Kawamori T, Wen X, Tsuji PA, Walle UK. Cancer chemopreventive properties of orally bioavailable flavonoids-methylated versus unmethylated flavones. Biochem Pharmacol 2007;73:1288-96.  Back to cited text no. 108
109.Seibert H, Maser E, Schweda K, Seibert S, Gülden M. Cytoprotective activity against peroxide-induced oxidative damage and cytotoxicity of flavonoids in C6 rat glioma cells. Food Chem Toxicol 2011;49:2398-407.  Back to cited text no. 109
110.Iwuchukwu OF, Tallarida RJ, Nagar S. Resveratrol in combination with other dietary polyphenols concomitantly enhances antiproliferation and UGT1A1 induction in Caco-2 cells. Life Sci 2011;88:1047-54.  Back to cited text no. 110
111.Sun F, Zheng XY, Ye J, Wu TT, Wang JI, Chen W. Potential anticancer activity of myricetin in human T24 bladder cancer cells both in vitro and in vivo. Nutr Cancer 2012;64:599-606.  Back to cited text no. 111
112.Rodgers EH, Grant MH. The effect of the flavonoids, quercetin, myricetin and epicatechin on the growth and enzyme activities of MCF7 human breast cancer cells. Chem Biol Interact 1998;116:213-28.  Back to cited text no. 112
113.Forni C, Braglia R, Lentini A, Nuccetelli M, Provenzano B, Tabolacci C, et al. Role of transglutaminase 2 in quercetin-induced differentiation of B16-F10 murine melanoma cells. Amino Acids 2009;36:731-8.  Back to cited text no. 113
114.Nagao T, Abe F, Kinjo J, Okabe H. Antiproliferative constituents in plants 10. Flavones from the leaves of Lantana montevidensis Briq. and consideration of structure-activity relationship. Biol Pharm Bull 2002;25:875-9.  Back to cited text no. 114
115.Himeji M, Ohtsuki T, Fukazawa H, Tanaka M, Yazaki S, Ui S, et al. Difference of growth-inhibitory effect of Scutellaria baicalensis-producing flavonoid wogonin among human cancer cells and normal diploid cell. Cancer Lett 2007;245:269-74.  Back to cited text no. 115
116.Ikezoe T, Chen SS, Heber D, Taguchi H, Koeffler HP. Baicalin is a major component of PC-SPES which inhibits the proliferation of human cancer cells via apoptosis and cell cycle arrest. Prostate 2001;49:285-92.  Back to cited text no. 116
117.Bonham M, Posakony J, Coleman I, Montgomery B, Simon J, Nelson PS, et al. Characterization of chemical constituents in Scutellaria baicalensis with antiandrogenic and growth-inhibitory activities toward prostate carcinoma. Clin Cancer Res 2005;11:3905-14.  Back to cited text no. 117
118.Zheng Q, Hirose Y, Yoshimi N, Murakami A, Koshimizu K, Ohigashi H, et al. Further investigation of the modifying effect of various chemopreventive agents on apoptosis and cell proliferation in human colon cancer cells. J Cancer Res Clin Oncol 2002;128:539-46.  Back to cited text no. 118
119.Chen CH, Huang LL, Huang CC, Lin CC, Lee Y, Lu FJ. Baicalein, a novel apoptotic agent for hepatoma cell lines: A potential medicine for hepatoma. Nutr Cancer 2000;38:287-95.  Back to cited text no. 119
120.Kuo SM. Antiproliferative potency of structurally distinct dietary flavonoids on human colon cancer cells. Cancer Lett 1996;110:41-8.  Back to cited text no. 120
121.Hong TB, Rahumatullah A, Yogarajah T, Ahmad M, Yin KB. Potential effects of chrysin on MDA-MB-231 cells. Int J Mol Sci 2010;11:1057-69.  Back to cited text no. 121
122.Yang SF, Yang WE, Chang HR, Chu SC, Hsieh YS. Luteolin induces apoptosis in oral squamous cancer cells. J Dent Res 2008;87:401-6.  Back to cited text no. 122
123.Wu B, Zhang Q, Shen W, Zhu J. Anti-proliferative and chemosensitizing effects of luteolin on human gastric cancer AGS cell line. Mol Cell Biochem 2008;313:125-32.  Back to cited text no. 123
124.Patil JR, Chidambara Murthy KN, Jayaprakasha GK, Chetti MB, Patil BS. Bioactive compounds from Mexican lime (Citrus aurantifolia) juice induce apoptosis in human pancreatic cells. J Agric Food Chem 2009;57:10933-42.  Back to cited text no. 124
125.Li W, Du B, Wang T, Wang S, Zhang J. Kaempferol induces apoptosis in human HCT116 colon cancer cells via the Ataxia-Telangiectasia Mutated-p53 pathway with the involvement of p53 Upregulated Modulator of Apoptosis. Chem Biol Interact 2009;177:121-7.  Back to cited text no. 125
126.Luo H, Rankin GO, Li Z, Depriest L, Chen YC. Kaempferol induces apoptosis in ovarian cancer cells through activating p53 in the intrinsic pathway. Food Chem 2011;128:513-9.  Back to cited text no. 126
127.Wang W, Heideman L, Chung CS, Pelling JC, Koehler KJ, Birt DF. Cell-cycle arrest at G2/M and growth inhibition by apigenin in human colon carcinoma cell lines. Mol Carcinog 2000;28:102-10.  Back to cited text no. 127
128.Sivagami G, Vinothkumar R, Preethy CP, Riyasdeen A, Akbarsha MA, Menon VP, et al. Role of hesperetin (a natural flavonoid) and its analogue on apoptosis in HT-29 human colon adenocarcinoma cell line: A comparative study. Food Chem Toxicol 2012;50:660-71.  Back to cited text no. 128
129.You HJ, Ahn HJ, Ji GE. Transformation of rutin to antiproliferative quercetin-3-glucoside by Aspergillus niger. J Agric Food Chem 2010;58:10886-92.  Back to cited text no. 129
130.Cai J, Zhao XL, Liu AW, Nian H, Zhang SH. Apigenin inhibits hepatoma cell growth through alteration of gene expression patterns. Phytomedicine 2011;18:366-73.  Back to cited text no. 130
131.Wei L, Lu N, Dai Q, Rong J, Chen Y, Li Z, et al. Different apoptotic effects of wogonin via induction of H(2)O(2) generation and Ca(2+) overload in malignant hepatoma and normal hepatic cells. J Cell Biochem 2010;111:1629-41.  Back to cited text no. 131
132.Xu M, Lu N, Zhang H, Dai Q, Wei L, Li Z, et al. Wogonin induced cytotoxicity in human hepatocellular carcinoma cells by activation of unfolded protein response and inactivation of AKT. Hepatol Res 2013;43:890-905.  Back to cited text no. 132
133.Romanouskaya TV, Grinev VV. Cytotoxic effect of flavonoids on leukemia cells and normal cells of human blood. Bull Exp Biol Med 2009;148:57-9.  Back to cited text no. 133
134.Jang KY, Jeong SJ, Kim SH, Jung JH, Kim JH, Koh W, et al. Activation of reactive oxygen species/AMP activated protein kinase signaling mediates fisetin-induced apoptosis in multiple myeloma U266 cells. Cancer Lett 2012;319:197-202.  Back to cited text no. 134
135.Baumann S, Fas SC, Giaisi M, Müller WW, Merling A, Gülow K, et al. Wogonin preferentially kills malignant lymphocytes and suppresses T-cell tumor growth by inducing PLCgamma1- and Ca 2+-dependent apoptosis. Blood 2008;111:2354-63.  Back to cited text no. 135
136.Guthrie N, Gapor A, Chambers AF, Carroll KK. Palm oil tocotrienols and plant flavonoids act synergistically to inhibit proliferation of estrogen receptor-negative MDA-MB-231 and -positive MCF-7 human breast cancer cells in culture. Asia Pacific J Clin Nutr 1997;6:41-5.  Back to cited text no. 136
137.Wang LM, Xie KP, Huo HN, Shang F, Zou W, Xie MJ. Luteolin inhibits proliferation induced by IGF-1 pathway dependent ERα in human breast cancer MCF-7 cells. Asian Pac J Cancer Prev 2012;13:1431-7.  Back to cited text no. 137
138.Kim MJ, Woo JS, Kwon CH, Kim JH, Kim YK, Kim KH. Luteolin induces apoptotic cell death through AIF nuclear translocation mediated by activation of ERK and p38 in human breast cancer cell lines. Cell Biol Int 2012;36:339-44.  Back to cited text no. 138
139.Long X, Fan M, Bigsby RM, Nephew KP. Apigenin inhibits antiestrogen-resistant breast cancer cell growth through estrogen receptor-alpha-dependent and estrogen receptor-alpha-independent mechanisms. Mol Cancer Ther 2008;7:2096-108.  Back to cited text no. 139
140.Britton RG, Horner-Glister E, Pomenya OA, Smith EE, Denton R, Jenkins PR, et al. Synthesis and biological evaluation of novel flavonols as potential anti-prostate cancer agents. Eur J Med Chem 2012;54:952-8.  Back to cited text no. 140
141.Kim JY, Jeon YK, Jeon W, Nam MJ. Fisetin induces apoptosis in Huh-7 cells via downregulation of BIRC8 and Bcl2L2. Food Chem Toxicol 2010;48:2259-64.  Back to cited text no. 141
142.Khan N, Asim M, Afaq F, Abu Zaid M, Mukhtar H. A novel dietary flavonoid fisetin inhibits androgen receptor signaling and tumor growth in athymic nude mice. Cancer Res 2008;68:8555-63.  Back to cited text no. 142
143.Seo YJ, Kim BS, Chun SY, Park YK, Kang KS, Kwon TG. Apoptotic effects of genistein, biochanin-A and apigenin on LNCaP and PC-3 cells by p21 through transcriptional inhibition of polo-like kinase-1. J Korean Med Sci 2011;26:1489-94.  Back to cited text no. 143
144.Chen S, Ruan Q, Bedner E, Deptala A, Wang X, Hsieh TC, et al. Effects of the flavonoid baicalin and its metabolite baicalein on androgen receptor expression, cell cycle progression and apoptosis of prostate cancer cell lines. Cell Prolif 2001;34:293-304.  Back to cited text no. 144
145.Pan MH, Chen WJ, Lin-Shiau SY, Ho CT, Lin JK. Tangeretin induces cell-cycle G1 arrest through inhibiting cyclin-dependent kinases 2 and 4 activities as well as elevating Cdk inhibitors p21 and p27 in human colorectal carcinoma cells. Carcinogenesis 2002;23:1677-84.  Back to cited text no. 145
146.Yang J, Liu RH. Synergistic effect of apple extracts and quercetin 3-beta-d-glucoside combination on antiproliferative activity in MCF-7 human breast cancer cells in vitro. J Agric Food Chem 2009;57:8581-6.  Back to cited text no. 146
147.Parajuli P, Joshee N, Rimando AM, Mittal S, Yadav AK. In vitro antitumor mechanisms of various Scutellaria extracts and constituent flavonoids. Planta Med 2009;75:41-8.  Back to cited text no. 147
148.Skupień K, Oszmiański J, Kostrzewa-Nowak D, Tarasiuk J. In vitro antileukaemic activity of extracts from berry plant leaves against sensitive and multidrug resistant HL60 cells. Cancer Lett 2006;236:282-91.  Back to cited text no. 148
149.Lu HF, Chie YJ, Yang MS, Lee CS, Fu JJ, Yang JS, et al. Apigenin induces caspase-dependent apoptosis in human lung cancer A549 cells through Bax- and Bcl-2-triggered mitochondrial pathway. Int J Oncol 2010;36:1477-84.  Back to cited text no. 149
150.Chen WY, Hsieh YA, Tsai CI, Kang YF, Chang FR, Wu YC, et al. Protoapigenone, a natural derivative of apigenin, induces mitogen-activated protein kinase-dependent apoptosis in human breast cancer cells associated with induction of oxidative stress and inhibition of glutathione S-transferase TT. Invest New Drugs 2011;29:1347-59.  Back to cited text no. 150
151.Strouch MJ, Milam BM, Melstrom LG, McGill JJ, Salabat MR, Ujiki MB, et al. The flavonoid apigenin potentiates the growth inhibitory effects of gemcitabine and abrogates gemcitabine resistance in human pancreatic cancer cells. Pancreas 2009;38:409-15.  Back to cited text no. 151
152.Sak K. Site-specific anticancer effects of dietay flavonoid quercetin. Nutr Cancer 2014;66:177-93.  Back to cited text no. 152
153.Suh Y, Afaq F, Johnson JJ, Mukhtar H. A plant flavonoid fisetin induces apoptosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kappaB signaling pathways. Carcinogenesis 2009;30:300-7.  Back to cited text no. 153
154.Syed DN, Afaq F, Maddodi N, Johnson JJ, Sarfaraz S, Ahmad A, et al. Inhibition of human melanoma cell growth by the dietary flavonoid fisetin is associated with disruption of Wnt/β-catenin signaling and decreased Mitf levels. J Invest Dermatol 2011;131:1291-9.  Back to cited text no. 154
155.Lim do Y, Park JH. Induction of p53 contributes to apoptosis of HCT-116 human colon cancer cells induced by the diteary compound fisetin. Am J Physiol Gastrointest Liver Physiol 2009;296:G1060-8.  Back to cited text no. 155
156.Khan N, Afaq F, Khusro FH, Mustafa Adhami V, Suh Y, Mukhtar H. Dual inhibition of phosphatidylinositol 3-kinase/Akt and mammalian target of rapamycin signaling in human nonsmall cell lung cancer cells by a dietay flavonoid fisetin. Int J Cancer. 2012;130:1695-705.  Back to cited text no. 156
157.Khan N, Afaq F, Syed DN, Mukhtar H. Fisetin, a novel dietary flavonoid, causes apoptosis and cell cycle arrest in human prostate cancer LNCaP cells. Carcinogenesis 2008;29:1049-56.  Back to cited text no. 157
158.Haddad AQ, Fleshner N, Nelson C, Saour B, Musquera M, Venkateswaran V, et al. Antiproliferative mechanisms of the flavonoids 2,2`-dihydroxychalcone and fisetin in human prostate cancer cells. Nutr Cancer 2010;62:668-81.  Back to cited text no. 158
159.Zhang W, Lan Y, Huang Q, Hua Z. Galangin induces B16F10 melanoma cell apoptosis via mitochondrial pathway and sustained activation of p38 MAPK. Cytotechnology 2013;65:447-55.  Back to cited text no. 159
160.Murray TJ, Yang X, Sherr DH. Growth of a human mammary tumor cell line is blocked by galangin, a naturally occurring bioflavonoid, and is accompanied by down-regulation of cyclins D3, E, and A. Breast Cancer Res 2006;8:R17.  Back to cited text no. 160
161.Hernandez J, Goycoolea FM, Quintero J, Acosta A, Castaneda M, Dominguez Z, et al. Sonoran propolis: Chemical composition and antiproliferative activity on cancer cell lines. Planta Med 2007;73:1469-74.  Back to cited text no. 161
162.Bestwick CS, Milne L, Duthie SJ. Kaempferol induced inhibition of HL-60 cell growth results from a heterogeneous response, dominated by cell cycle alterations. Chem Biol Interact 2007;170:76-85.  Back to cited text no. 162
163.Ackland ML, van de Waarsenburg S, Jones R. Synergistic antiproliferative action of the flavonols quercetin and kaempferol in cultured human cancer cell lines. In Vivo 2005;19:69-76.  Back to cited text no. 163
164.Fabjan N, Rode J, Kosir IJ, Wang Z, Zhang Z, Kreft I. Tartary buckwheat (Fagopyrum tataricum Gaertn.) as a course of dietary rutin and quercitrin. J Agric Food Chem 2003;51:6452-5.  Back to cited text no. 164
165.Mämmelä P, Savolainen H, Lindroos L, Kangas J, Vartiainen T. Analysis of oak tannins by liquid chromatography-electrospray ionisation mass spectrometry. J Chromatogr A 2000;891:75-83.  Back to cited text no. 165
166.Jiang S, Yang J, Qian D, Guo J, Shang EX, Duan JA, et al. Rapid screening and identification of metabolites of quercitrin produced by the human intestinal bacteria using ultra performance liquid chromatography/quadrupole-time-of-flight mass spectrometry. Arch Pharm Res 2014;37:204-13.  Back to cited text no. 166
167.Thani W, Vallisuta O, Siripong P, Ruangwises N. Anti-proliferative and antioxidative activities of Thai noni/Yor (Morinda citrifolia Linn.) leaf extract. Southeast Asian J Trop Med Public Health 2010;41:482-9.  Back to cited text no. 167
168.Lee ER, Kang YJ, Kim HJ, Choi HY, Kang GH, Kim JH, et al. Regulation of apoptosis by modified naringenin derivatives in human colorectal carcinoma RKO cells. J Cell Biochem 2008;104:259-73.  Back to cited text no. 168
169.Frydoonfar HR, McGrath DR, Spigelman AD. The variable effect on proliferation of a colon cancer cell line by the citrus fruit flavonoid Naringenin. Colorectal Dis 2003;5:149-52.  Back to cited text no. 169
170.Alshatwi AA, Hasan TN, Shafi G, Alsaif MA, Al-Hazzani AA, Alsaif AA. A single-nucleotide polymorphism in the TP53 and MDM-2 gene modifies breast cancer risk in an ethnic Arab population. Fundam Clin Pharmacol 2012;26:438-43.  Back to cited text no. 170
171.Zarebczan B, Pinchot SN, Kunnimalaiyaan M, Chen H. Hesperetin, a potential therapy for carcinoid cancer. Am J Surg 2011;201:329-32.  Back to cited text no. 171
172.Quintin J, Buisson D, Thoret S, Cresteil T, Lewin G. Semisynthesis and antiproliferative evaluation of a series of 3`-aminoflavones. Bioorg Med Chem Lett 2009;19:3502-6.  Back to cited text no. 172
173.Pereira RM, Andrades NE, Paulino N, Sawaya AC, Eberlin MN, Marcucci MC, et al. Synthesis and characterization of a metal complex containing naringin and Cu, and its antioxidant, antimicrobial, antiinflammatory and tumor cell cytotoxicity. Molecules 2007;12:1352-66.  Back to cited text no. 173
174.Zandi K, Teoh BT, Sam SS, Wong PF, Mustafa MR, Abubakar S. Antiviral activity of four types of bioflavonoid against dengue virus type-2. Virol J 2011;8:560.  Back to cited text no. 174
175.Wesolowska O, Wisniewski J, Sroda-Pomianek K, Bielawska-Pohl A, Paprocka M, Duś D, et al. Multidrug resistance reversal and apoptosis induction in human colon cancer cells by some flavonoids present in Citrus plants. J Nat Prod 2012;75:1896-902.  Back to cited text no. 175
176.Nazari M, Ghorbani A, Hekmat-Doost A, Jeddi-Tehrani M, Zand H. Inactivation of nuclear factor-kB by citrus flavanone hesperidin contributes to apoptosis and chemo-sensitizing effect in Ramos cells. Eur J Pharmacol 2011;650:526-33.  Back to cited text no. 176
177.Al-Ashaal HA, El-Sheltawy ST. Antioxidant capacity of hesperidin from citrus peel using electron spin resonance and cytotoxic activity against human carcinoma cell lines. Pharm Biol 2011;49:276-82.  Back to cited text no. 177
178.Lee WJ, Chen WK, Wang CJ, Lin WL, Tseng TH. Apigenin inhibits HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and beta 4 integrin function in MDA-MB-231 breast cancer cells. Toxicol Appl Pharmacol 2008;226:178-91.  Back to cited text no. 178
179.Gupta S, Afaq F, Mukhtar H. Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells. Oncogene 2002;21:3727-38.  Back to cited text no. 179
180.Choi SI, Jeong CS, Cho SY, Lee YS. Mechanism of apoptosis induced by apigenin in HepG2 human hepatoma cells: Involvement of reactive oxygen species generated by NADPH oxidase. Arch Pharm Res 2007;30:1328-35.  Back to cited text no. 180
181.Mak P, Leung YK, Tang WY, Harwood C, Ho SM. Apigenin suppresses cancer cell growth through ERbeta. Neoplasia 2006;8:896-904.  Back to cited text no. 181
182.Lu HF, Chie YJ, Yang MS, Lu KW, Fu JJ, Yang JS, et al. Apigenin induces apoptosis in human lung cancer H460 cells through caspase- and mitochondria-dependent pathways. Hum Exp Toxicol 2011;30:1053-61.  Back to cited text no. 182
183.Wu B, Li J, Huang D, Wang W, Chen Y, Liao Y, et al. Baicalein mediates inhibition of migration and invasiveness of skin carcinoma through Ezrin in A431 cells. BMC Cancer 2011;11:527.  Back to cited text no. 183
184.Zhang DY, Wu J, Ye F, Xue L, Jiang S, Yi J, et al. Inhibition of cancer cell proliferation and prostaglandin E2 synthesis by Scutellaria baicalensis. Cancer Res 2003;63:4037-43.  Back to cited text no. 184
185.Li QB, You Y, Chen ZC, Lü J, Shao J, Zou P. Role of Baicalein in the regulation of proliferation and apoptosis in human myeloma RPMI8226 cells. Chin Med J (Engl) 2006;119:948-52.  Back to cited text no. 185
186.Chou DS, Hsiao G, Lai YA, Tsai YJ, Sheu JR. Baicalein induces proliferation inhibition in B16F10 melanoma cells by generating reactive oxygen species via 12-lipoxygenase. Free Radic Biol Med 2009;46:1197-203.  Back to cited text no. 186
187.Weng MS, Ho YS, Lin JK. Chrysin induces G1 phase cell cycle arrest in C6 glioma cells through inducing p21Waf1/Cip1 expression: Involvement of p38 mitogen-activated protein kinase. Biochem Pharmacol 2005;69:1815-27.  Back to cited text no. 187
188.Pichichero E, Cicconi R, Mattei M, Muzi MG, Canini A. Acacia honey and chrysin reduce proliferation of melanoma cells through alterations in cell cycle progression. Int J Oncol 2010;37:973-81.  Back to cited text no. 188
189.Ren J, Cheng H, Xin WQ, Chen X, Hu K. Induction of apoptosis by 7-piperazinethylchrysin in HCT-116 human colon cancer cells. Oncol Rep 2012;28:1719-26.  Back to cited text no. 189
190.Tsui KH, Chung LC, Feng TH, Chang PL, Juang HH. Upregulation of prostate-derived Ets factor by luteolin causes inhibition of cell proliferation and cell invasion in prostate carcinoma cells. Int J Cancer 2012;130:2812-23.  Back to cited text no. 190
191.Chen KH, Weng MS, Lin JK. Tangeretin suppresses IL-1beta-induced cyclooxygenase (COX)-2 expression through inhibition of p38 MAPK, JNK, and AKT activation in human lung carcinoma cells. Biochem Pharmacol 2007;73:215-27.  Back to cited text no. 191
192.Zhang M, Liu LP, Chen Y, Tian XY, Qin J, Wang D, et al. Wogonin induces apoptosis in RPMI 8226, a human myeloma cell line, by downregulating phospho-Akt and overexpressing Bax. Life Sci 2013;92:55-62.  Back to cited text no. 192
193.Ciesielska E, Gwardys A, Metodiewa D. Anticancer, antiradical and antioxidative actions of novel Antoksyd S and its major components, baicalin and baicalein. Anticancer Res 2002;22:2885-91.  Back to cited text no. 193
194.Wang N, Tang LJ, Zhu GQ, Peng DY, Wang L, Sun FN, et al. Apoptosis induced by baicalin involving up-regulation of P53 and bax in MCF-7 cells. J Asian Nat Prod Res 2008;10:1129-35.  Back to cited text no. 194
195.Chowdhury SA, Kishino K, Satoh R, Hashimoto K, Kikuchi H, Nishikawa H, et al. Tumor-specificity and apoptosis-inducing activity of stilbenes and flavonoids. Anticancer Res 2005;25:2055-63.  Back to cited text no. 195
196.Katalinić M, Rusak G, Domaćinović Barović J, Sinko G, Jelić D, Antolović R, et al. Structural aspects of flavonoids as inhibitors of human butyrylcholinesterase. Eur J Med Chem 2010;45:186-92.  Back to cited text no. 196
197.Monasterio A, Urdaci MC, Pinchuk IV, Lopez-Moratalla N, Martinez-Irujo JJ. Flavonoids induce apoptosis in human leukemia U937 cells through caspase- and caspase-calpain-dependent pathways. Nutr Cancer 2004;50:90-100.  Back to cited text no. 197
198.Richter M, Ebermann R, Marian B. Quercetin-induced apoptosis in colorectal tumor cells: Possible role of EGF receptor signaling. Nutr Cancer 1999;34:88-99.  Back to cited text no. 198
199.Kuntz S, Wenzel U, Daniel H. Comparative analysis of the effects of flavonoids on proliferation, cytotoxicity, and apoptosis in human colon cancer cell lines. Eur J Nutr 1999;38:133-42.  Back to cited text no. 199
200.Lee SW, Lee JT, Lee MG, Lee HW, Ahn SJ, Lee YJ, et al. In vitro antiproliferative characteristics of flavonoids and diazepam on SNU-C4 colorectal adenocarcinoma cells. J Nat Med 2009;63:124-9.  Back to cited text no. 200
201.Kim DH, Lee JT, Lee IK, Ha JH. Comparative anticancer effects of flavonoids and diazepam in cultured cancer cells. Biol Pharm Bull 2008;31:255-9.  Back to cited text no. 201
202.Murtaza I, Adhami VM, Hafeez BB, Saleem M, Mukhtar H. Fisetin, a natural flavonoid, targets chemoresistant human pancreatic cancer AsPC-1 cells through DR3-mediated inhibition of NF-kappaB. Int J Cancer 2009;125:2465-73.  Back to cited text no. 202
203.Haddad AQ, Venkateswaran V, Viswanathan L, Teahan SJ, Fleshner NE, Klotz LH. Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines. Prostate Cancer Prostatic Dis 2006;9:68-76.  Back to cited text no. 203
204.Ludwiczuk A, Saha A, Kuzuhara T, Asakawa Y. Bioactivity guided isolation of anticancer constituents from leaves of Alnus sieboldiana (Betulaceae). Phytomedicine 2011;18:491-8.  Back to cited text no. 204
205.Brown J, O`Prey J, Harrison PR. Enhanced sensitivity of human oral tumours to the flavonol, morin, during cancer progression: Involvement of the Akt and stress kinase pathways. Carcinogenesis 2003;24:171-7.  Back to cited text no. 205
206.Li F, Awale S, Tezuka Y, Esumi H, Kadota S. Study on the constituents of Mexican propolis and their cytotoxic activity against PANC-1 human pancreatic cancer cells. J Nat Prod 2010;73:623-7.  Back to cited text no. 206
207.Bai N, He K, Roller M, Lai CS, Shao X, Pan MH, et al. Flavonoids and phenolic compounds from Rosmarinus officinalis. J Argic Food Chem 2010;58:5363-7.  Back to cited text no. 207
208.Dickancaité E, Nemeikaitè A, Kalvelytè A, Cènas N. Prooxidant character of flavonoid cytotoxicity: Structure-activity relationships. Biochem Mol Biol Int 1998;45:923-30.  Back to cited text no. 208
209.Lin CM, Chen CT, Lee HH, Lin JK. Prevention of cellular ROS damage by isovitexin and related flavonoids. Planta Med 2002;68:365-7.  Back to cited text no. 209
210.Rusak G, Gutzeit HO, Müller JL. Structurally related flavonoids with antioxidative properties differentially affect cell cycle progression and apoptosis of human acute leukemia cells. Nutr Res 2005;25:143-55.  Back to cited text no. 210
211.Rao YK, Geethangili M, Fang SH, Tzeng YM. Antioxidant and cytotoxic activities of naturally occurring phenolic and related compounds: A comparative study. Food Chem Toxicol 2007;45:1770-6.  Back to cited text no. 211
212.Bigović D, Savikin K, Janković T, Menković N, Zdunić G, Stanojković T, et al. Antiradical and cytotoxic activity of different Helichrysum plicatum flower extracts. Nat Prod Commun 2011;6:819-22.  Back to cited text no. 212
213.Huang WW, Chiu YJ, Fan MJ, Lu HF, Yeh HF, Li KH, et al. Kaempferol induced apoptosis via endoplasmic reticulum stress and mitochondria-dependent pathway in human osteosarcoma U-2 OS cells. Mol Nutr Food Res 2010;54:1585-95.  Back to cited text no. 213
214.Wang C, Kurzer MS. Phytoestrogen concentration determines effects on DNA synthesis in human breast cancer cells. Nutr Cancer 1997;28:236-47.  Back to cited text no. 214
215.Balabhadrapathruni S, Thomas TJ, Yurkow EJ, Amenta PS, Thomas T. Effects of genistein and structurally related phytoestrogens on cell cycle kinetics and apoptosis in MDA-MB-468 human breast cancer cells. Oncol Rep 2000;7:3-12.  Back to cited text no. 215
216.Phromnoi K, Yodkeeree S, Anuchapreeda S, Limtrakul P. Inhibition of MMP-3 activity and invasion of the MDA-MB-231 human invasive breast carcinoma cell line by bioflavonoids. Acta Pharmacol Sin 2009;30:1169-76.  Back to cited text no. 216
217.Manthey JA, Guthrie N. Antiproliferative activities of citrus flavonoids against six human cancer cell lines. J Argic Food Chem 2002;50:5837-43.  Back to cited text no. 217
218.Loizzo MR, Said A, Tundis R, Hawas UW, Rashed K, Menichini F, et al. Antioxidant and antiproliferative activity of Diospyros lotus L. extract and isolated compounds. Plant Foods Hum Nutr 2009;64:264-70.  Back to cited text no. 218
219.Kim YK, Kim YS, Choi SU, Ryu SY. Isolation of flavonol rhamnosides from Loranthus tanakae and cytotoxic effect of them on human tumor cell lines. Arch Pharm Res 2004;27:44-7.  Back to cited text no. 219
220.Kwak JH, Kang MW, Roh JH, Choi SU, Zee OP. Cytotoxic phenolic compounds from Chionanthus retusus. Arch Pharm Res 2009;32:1681-7.  Back to cited text no. 220
221.Loa J, Chow P, Zhang K. Studies of structure-activity relationship on plant polyphenol-induced suppression of human liver cancer cells. Cancer Chemother Pharmacol 2009;63:1007-16.  Back to cited text no. 221
222.Said A, Tundis R, Hawas UW, El-Kousy SM, Rashed K, Menichini F, et al. In vitro antioxidant and antiproliferative activities of flavonoids from Ailanthus excelsa (Roxb.) (Simaroubaceae) leaves. Z Naturforsch C 2010;65:180-6.  Back to cited text no. 222
223.Nguyen TT, Tran E, Ong CK, Lee SK, Do PT, Huynh TT, et al. Kaempferol-induced growth inhibition and apoptosis in A549 lung cancer cells is mediated by activation of MEK-MAPK. J Cell Physiol 2003;197:110-21.  Back to cited text no. 223
224.Casagrande F, Darbon JM. Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: Regulation of cyclin-dependent kinases CDK2 and CDK1. Biochem Pharmacol 2001;61:1205-15.  Back to cited text no. 224
225.O`Prey J, Brown J, Fleming J, Harrison PR. Effects of dietary flavonoids on major signal transduction pathways in human epithelial cells. Biochem Pharmacol 2003;66:2075-88.  Back to cited text no. 225
226.Zhang Q, Zhao XH, Wang ZJ. Flavones and flavonols exert cytotoxic effects on a human oesophageal adenocarcinoma cell line (OE33) by causing G2/M arrest and inducing apoptosis. Food Chem Toxicol 2008;46:2042-53.  Back to cited text no. 226
227.Zhang Q, Zhao XH, Wang ZJ. Cytotoxicity of flavones and flavonols to a human oesophageal squamous cell carcinoma cell line (KYSE-510) by induction of G2/M arrest and apoptosis. Toxicol In Vitro 2009;23:797-807.  Back to cited text no. 227
228.Kawaii S, Tomono Y, Katase E, Ogawa K, Yano M. Antiproliferative activity of flavonoids on several cancer cell lines. Biosci Biotechnol Biochem 1999;63:896-9.  Back to cited text no. 228
229.Freire AC, da Silva Melo P, Aoyama H, Haun M, Durán N, Ferreira CV. Cytotoxic effect of the diterpene lactone dehydrocrotonin from Croton cajucara on human promyelocytic leukemia cells. Planta Med 2003;69:67-9.  Back to cited text no. 229
230.Aherne SA, O`Brien NM. Protection by the flavonoids myricetin, quercetin, and rutin against hydrogen peroxide-induced DNA damage in Caco-2 and Hep G2 cells. Nutr Cancer 1999;34:160-6.  Back to cited text no. 230
231.Newell AM, Yousef GG, Lila MA, Ramirez-Mares MV, de Mejia EG. Comparative in vitro bioactivities of tea extracts from six species of Ardisia and their effect on growth inhibition of HepG2 cells. J Ethnopharmacol 2010;130:536-44.  Back to cited text no. 231
232.Yáñez J, Vicente V, Alcaraz M, Castillo J, Benavente-García O, Canteras M, et al. Cytotoxicity and antiproliferative activities of several phenolic compounds against three melanocytes cell lines: Relationship between structure and activity. Nutr Cancer 2004;49:191-9.  Back to cited text no. 232
233.Xu R, Zhang Y, Ye X, Xue S, Shi J, Pan J, et al. Inhibition effects and induction of apoptosis of flavonoids on the prostate cancer cell line PC-3 in vitro. Food Chem 2013;138:48-53.  Back to cited text no. 233
234.Lohezic-Le Dehevat F, Tomasi S, Fontanel D, Boustie J. Flavonols from Scurrula Ferruginea Danser (Loranthaceae). Z Naturforsch C 2002;57:1092-5.  Back to cited text no. 234
235.Simirgiotis MJ, Adachi S, To S, Yang H, Reynertson KA, Basile MJ, et al. Cytotoxic chalcones and antioxidants from the fruits of a Syzygium samarangense (Wax Jambu). Food Chem 2008;107:813-9.  Back to cited text no. 235
236.Browning AM, Walle UK, Walle T. Flavonoid glycosides inhibit oral cancer cell proliferation - role of cellular uptake and hydrolysis to the aglycones. J Pharm Pharmacol 2005;57:1037-42.  Back to cited text no. 236
237.Chao JI, Su WC, Liu HF. Baicalein induces cancer cell death and proliferation retardation by the inhibition of CDC2 kinase and survivin associated with opposite role of p38 mitogen-activated protein kinase and AKT. Mol Cancer Ther 2007;6:3039-48.  Back to cited text no. 237
238.Ramanathan R, Tan CH, Das NP. Cytotoxic effect of plant polyphenols and fat-soluble vitamins on malignant human cultured cells. Cancer Lett 1992;62:217-24.  Back to cited text no. 238
239.Chen YH, Chen HY, Hsu CL, Yen GC. Induction of apoptosis by the Lactuca indica L. in human leukemia cell line and its active components. J Agric Food Chem 2007;55:1743-9.  Back to cited text no. 239
240.Rhouma GB, Chebil L, Mustapha N, Krifa M, Ghedira K, Ghoul M, et al. Cytotoxic, genotoxic and antigenotoxic potencies of oligorutins. Hum Exp Toxicol 2013;32:881-9.  Back to cited text no. 240
241.Goniotaki M, Hatziantoniou S, Dimas K, Wagner M, Demetzos C. Encapsulation of naturally occurring flavonoids into liposomes: Physicochemical properties and biological activity against human cancer cell lines. J Pharm Pharmacol 2004;56:1217-24.  Back to cited text no. 241
242.Li L, Henry GE, Seeram NP. Identification and bioactivities of resveratrol oligomers and flavonoids from Carex folliculata seeds. J Agric Food Chem 2009;57:7282-7.  Back to cited text no. 242
243.Alía M, Mateos R, Ramos S, Lecumberri E, Bravo L, Goya L. Influence of quercetin and rutin on growth and antioxidant defense system of a human hepatoma cell line (HepG2). Eur J Nutr 2006;45:19-28.  Back to cited text no. 243
244.Bellocco E, Barreca D, Laganà G, Leuzzi U, Tellone E, Ficarra S, et al. Influence of L-rhamnosyl-D-glycosyl derivatives on properties and biological interaction of flavonoids. Mol Cell Biochem 2009;321:165-71.  Back to cited text no. 244
245.Ramos AA, Lima CF, Pereira ML, Fernandes-Ferreira M, Pereira-Wilson C. Antigenotoxic effects of quercetin, rutin and ursolic acid on HepG2 cells: Evaluation by the comet assay. Toxicol Lett 2008;177:66-73.  Back to cited text no. 245
246.Tsai YC, Lin CL, Chen BH. Preparative chromatography of flavonoids and saponins in Gynostemma pentaphyllum and their antiproliferation effect on hepatoma cell. Phytomedicine 2010;18:2-10.  Back to cited text no. 246
247.Wei XH, Yang SJ, Liang N, Hu DY, Jin LH, Xue W, et al. Chemical constituents of Caesalpinia decapetala (Roth) Alston. Molecules 2013;18:1325-36.  Back to cited text no. 247
248.Fang SC, Hsu CL, Lin HT, Yen GC. Anticancer effects of flavonoid derivatives isolated from Millettia reticulata Benth in SK-Hep-1 human hepatocellular carcinoma cells. J Agric Food Chem 2010;58:814-20.  Back to cited text no. 248
249.Moghaddam G, Ebrahimi SA, Rahbar-Roshandel N, Foroumadi A. Antiproliferative activity of flavonoids: Influence of the sequential methoxylation state of the flavonoid structure. Phytother Res 2012;26:1023-8.  Back to cited text no. 249
250.Hakimuddin F, Paliyath G, Meckling K. Selective cytotoxicity of a red grape wine flavonoid fraction against MCF-7 cells. Breast Cancer Res Treat 2004;85:65-79.  Back to cited text no. 250
251.Miranda CL, Stevens JF, Helmrich A, Henderson MC, Rodriguez RJ, Yang YH, et al. Antiproliferative and cytotoxic effects of prenylated flavonoids from hops (Humulus lupulus) in human cancer cell lines. Food Chem Toxicol 1999;37:271-85.  Back to cited text no. 251
252.So FV, Guthrie N, Chambers AF, Carroll KK. Inhibition of proliferation of estrogen receptor-positive MCF-7 human breast cancer cells by flavonoids in the presence and absence of excess estrogen. Cancer Lett 1997;112:127-33.  Back to cited text no. 252
253.Yelani T, Hussein AA, Meyer JJ. Isolation and identification of poisonous triterpenoids from Elaeodendron croceum. Nat Prod Res 2010;24:1418-25.  Back to cited text no. 253
254.So FV, Guthrie N, Chambers AF, Moussa M, Carroll KK. Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices. Nutr Cancer 1996;26:167-81.  Back to cited text no. 254
255.Jin CY, Park C, Hwang HJ, Kim GY, Choi BT, Kim WJ, et al. Naringenin up-regulates the expression of death receptor 5 and enhances TRAIL-induced apoptosis in human lung cancer A549 cells. Mol Nutr Food Res 2011;55:300-9.  Back to cited text no. 255
256.Jeon SH, Chun W, Choi YJ, Kwon YS. Cytotoxic constituents from the bark of Salix hulteni. Arch Pharm Res 2008;31:978-82.  Back to cited text no. 256
257.Alshatwi AA, Ramesh E, Periasamy VS, Subash-Babu P. The apoptotic effect of hesperetin on human cervical cancer cells is mediated through cell cycle arrest, death receptor, and mitochondrial pathways. Fundam Clin Pharmacol 2013;27:581-92.  Back to cited text no. 257
258.Lee CJ, Wilson L, Jordan MA, Nguyen V, Tang J, Smiyun G. Hesperidin suppressed proliferations of both human breast cancer and androgen-dependent prostate cancer cells. Phytother Res 2010;24 Suppl 1:S15-9.  Back to cited text no. 258
259.Ruela-de-Sousa RR, Fuhler GM, Blom N, Ferreira CV, Aoyama H, Peppelenbosch MP. Cytotoxicity of apigenin on leukemia cell lines: Implications for prevention and therapy. Cell Death Dis 2010;1:e19.  Back to cited text no. 259
260.Vargo MA, Voss OH, Poustka F, Cardounel AJ, Grotewold E, Doseff AI. Apigenin-induced-spoptosis is mediated by the activation of PKCdelta and caspases in leukemia cells. Biochem Pharmacol 2006;72:681-92.  Back to cited text no. 260
261.Sonoda M, Nishiyama T, Matsukawa Y, Moriyasu M. Cytotoxic activities of flavonoids from two Scutellaria plants in Chinese medicine. J Ethnopharmacol 2004;91:65-8.  Back to cited text no. 261
262.Zheng PW, Chaing LC, Lin CC. Apigenin induced apoptosis through p53-dependent pathway in human cervical carcinoma cells. Life Sci 2005;76:1367-79.  Back to cited text no. 262
263.Chen D, Landis-Piwowar KR, Chen MS, Dou QP. Inhibition of proteasome activity by the dietary flavonoid apigenin is associated with growth inhibition in cultured breast cancer cells and xenografts. Breast Cancer Res 2007;9:R80.  Back to cited text no. 263
264.Choi EJ, Kim GH. Apigenin induces apoptosis through a mitochondria/caspase-pathway in human breast cancer MDA-MB-453 cells. J Clin Biochem Nutr 2009;44:260-5.  Back to cited text no. 264
265.Choi EJ, Kim GH. 5-Fluorouracil combined with apigenin enhances anticancer activity through induction of apoptosis in human breast cancer MDA-MB-453 cells. Oncol Rep 2009;22:1533-7.  Back to cited text no. 265
266.Salama MM, Kandil ZA, Islam WT. Cytotoxic compounds from the leaves of Gaillardia aristata Pursh. growing in Egypt. Nat Prod Res 2012;26:2057-62.  Back to cited text no. 266
267.Forgo P, Zupkó I, Molnár J, Vasas A, Dombi G, Hohmann J. Bioactivity-guided isolation of antiproliferative compounds from Centaurea jacea L. Fitoterapia 2012;83:921-5.  Back to cited text no. 267
268.Hirano T, Oka K, Akiba M. Antiproliferative effects of synthetic and naturally occurring flavonoids on tumor cells of the human breast carcinoma cell line, ZR-75-1. Res Commun Chem Pathol Pharmacol 1989;64:69-78.  Back to cited text no. 268
269.Lindenmeyer F, Li H, Menashi S, Soria C, Lu H. Apigenin acts on the tumor cell invasion process and regulates protease production. Nutr Cancer 2001;39:139-47.  Back to cited text no. 269
270.Cardenas M, Marder M, Blank VC, Roguin LP. Antitumor activity of some natural flavonoids and synthetic derivatives on various human and murine cancer cell lines. Bioorg Med Chem 2006;14:2966-71.  Back to cited text no. 270
271.Csupor-Löffler B, Hajdú Z, Zupkó I, Molnár J, Forgo P, Vasas A, et al. Antiproliferative constituents of the roots of Conyza canadensis. Planta Med. 2011;77:1183-8.  Back to cited text no. 271
272.Csupor-Löffler B, Hajdú Z, Zupkó I, Réthy B, Falkay G, Forgo P, et al. Antiproliferative effect of flavonoids and sesquiterpenoids from Achillea millefolium s.l. on cultured human tumour cell lines. Phytother Res 2009;23:672-6.  Back to cited text no. 272
273.Csapi B, Hajdú Z, Zupkó I, Berényi A, Forgo P, Szabó P, et al. Bioactivity-guided isolation of antiproliferative compounds from Centaurea arenaria. Phytother Res 2010;24:1664-9.  Back to cited text no. 273
274.Fullas F, Hussain RA, Chai HB, Pezzuto JM, Soejarto DD, Kinghorn AD. Cytotoxic constituents of Baccharis gaudichaudiana. J Nat Prod 1994;57:801-7.  Back to cited text no. 274
275.Chiang LC, Ng LT, Lin IC, Kup PL, Lin CC. Anti-proliferative effect of apigenin and its apoptotic induction in human Hep G2 cells. Cancer Lett 2006;237:207-14.  Back to cited text no. 275
276.Yee SB, Lee JH, Chung HY, Im KS, Bae SJ, Choi JS, et al. Inhibitory effects of luteolin isolated from Ixeris sonchifolia Hance on the proliferation of HepG2 human hepatocellular carcinoma cells. Arch Pharm Res 2003;26:151-6.  Back to cited text no. 276
277.Das S, Sas J, Samadder A, Boujedaini N, Khuda-Bukhsh AR. Apigenin-induced apoptosis in A375 and A549 cells through selective action and dysfunction of mitochondria. Exp Biol Med (Maywood) 2012;237:1433-48.  Back to cited text no. 277
278.King JC, Lu QY, Li G, Moro A, Takahashi H, Chen M, et al. Evidence for activation of mutated p53 by apigenin in human pancreatic cancer. Biochim Biophys Acta 2012;1823:593-604.  Back to cited text no. 278
279.Ujiki MB, Ding XZ, Salabat MR, Bentrem DJ, Golkar L, Milam B, et al. Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle arrest. Mol Cancer 2006;5:76.  Back to cited text no. 279
280.Shukla S, Gupta S. Apigenin-induced prostate cancer cell death is initiated by reactive oxygen species and p53 activation. Free Radic Biol Med 2008;44:1833-45.  Back to cited text no. 280
281.Shenouda NS, Zhou C, Browning JD, Ansell PJ, Sakla MS, Lubahn DB, et al. Phytoestrogens in common herbs regulate prostate cancer cell growth in vitro. Nutr Cancer 2004;49:200-8.  Back to cited text no. 281
282.Chen SS, Corteling R, Stevanato L, Sinden J. Polyphenols inhibit indoleamine 3,5-dioxygenase-1 enzymatic activity: A role of immunomodulation in chemoprevention. Discov Med 2012;14:327-33.  Back to cited text no. 282
283.Cherng JM, Shieh DE, Chiang W, Chang MY, Chiang LC. Chemopreventive effects of minor dietary constituents in common foods on human cancer cells. Biosci Biotechnol Biochem 2007;71:1500-4.  Back to cited text no. 283
284.Roy MK, Nakahara K, Na TV, Trakoontivakorn G, Takenaka M, Isobe S, et al. Baicalein, a flavonoid extracted from a metanolic extract of Oroxylum indicum inhibits proliferation of a cancer cell line in vitro via induction of apoptosis. Pharmazie 2007;62:149-53.  Back to cited text no. 284
285.Ma Z, Otsuyama K, Liu S, Abroun S, Ishikawa H, Tsuyama N, et al. Baicalein, a component of Scutellaria radix from Huang-Lian-Jie-Du-Tang (HLJDT), leads to suppression of proliferation and induction of apoptosis in human myeloma cells. Blood 2005;105:3312-8.  Back to cited text no. 285
286.Ciesielska E, Wolszczak M, Gulanowski B, Szulawska A, Kochman A, Metodiewa D. In vitro antileukemic, antioxidant and prooxidant activities of Antoksyd S (C/E/XXI): A comparison with baicalin and baicalein. In Vivo 2004;18:497-503.  Back to cited text no. 286
287.Ishii K, Tanaka S, Kagami K, Henmi K, Toyoda H, Kaise T, et al. Effects of naturally occurring polymethoxyflavonoids on cell growth, p-glycoprotein function, cell cycle, and apoptosis of daunorubicin-resistant T lymphoblastoid leukemia cells. Cancer Invest 2010;28:220-9.  Back to cited text no. 287
288.Austin CA, Patel S, Ono K, Nakane H, Fisher LM. Site-specific DNA cleavage by mammalian DNA topoisomerase II induced by novel flavone and catechin derivatives. Biochem J 1992;282:883-9.  Back to cited text no. 288
289.Bednar W, Holzmann K, Marian B. Assessing 12(S)-lipoxygenase inhibitory activity using colorectal cancer cells overexpressing the enzyme. Food Chem Toxicol 2007;45:508-14.  Back to cited text no. 289
290.Liang RR, Zhang S, Qi JA, Wang ZD, Li J, Liu PJ, et al. Preferential inhibition of hepatocellular carcinoma by the flavonoid Baicalein through blocking MEK-ERK signaling. Int J Oncol 2012;41:969-78.  Back to cited text no. 290
291.Matsuzaki Y, Kurokawa N, Terai S, Matsumura Y, Kobayashi N, Okita K. Cell death induced by baicalein in human hepatocellular carcinoma cell lines. Jpn J Cancer Res 1996;87:170-7.  Back to cited text no. 291
292.Motoo Y, Sawaby N. Antitumor effects of saikosaponins, baicalin and baicalein on human hepatoma cell lines. Cancer Lett 1994;86:91-5.  Back to cited text no. 292
293.Leung HW, Yang WH, Lai MY, Lin CJ, Lee HZ. Inhibition of 12-lipoxygenase during baicalein-induced human lung nonsmall carcinoma H460 cell apoptosis. Food Chem Toxicol 2007;45:403-11.  Back to cited text no. 293
294.Boik JC, Newman RA. A classification model to predict synergism/antagonism of cytotoxic mixtures using protein-drug docking scores. BMC Pharmacol 2008;8:13.  Back to cited text no. 294
295.Cheng YH, Li LA, Lin P, Cheng LC, Hung CH, Chang NW, et al. Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation. Toxicol Appl Pharmacol 2012;263:360-7.  Back to cited text no. 295
296.Pidgeon GP, Kandouz M, Meram A, Honn KV. Mechanisms controlling cell cycle arrest and induction of apoptosis after 12-lipoxygenase inhibition in prostate cancer cells. Cancer Res 2002;62:2721-7.  Back to cited text no. 296
297.Pilátová M, Stupáková V, Varinská L, Sarisský M, Mirossay L, Mirossay A, et al. Effect of selected flavones on cancer and endothelial cells. Gen Physiol Biophys 2010;29:134-43.  Back to cited text no. 297
298.Ai XH, Zheng X, Tang XQ, Sun L, Zhang YQ, Qin Y, et al. Induction of apoptosis of human gastric carcinoma SGC-7901 cell line by 5,7-dihydroxy-8-nitrochrysin in vitro. World J Gastroenterol 2007;13:3824-8.  Back to cited text no. 298
299.Zhang T, Chen X, Qu L, Wu J, Cui R, Zhao Y. Chrysin and its phosphate ester inhibit cell proliferation and induce apoptosis in Hela cells. Bioorg Med Chem 2004;12:6097-105.  Back to cited text no. 299
300.Lyu SY, Park WB. Production of cytokine and NO by RAW 264.7 macrophages and PBMC in vitro incubation with flavonoids. Arch Pharm Res 2005;28:573-81.  Back to cited text no. 300
301.Kilani-Jaziri S, Neffati A, Limem I, Boubaker J, Skandrani I, Sghair MB, et al. Relationship correlation of antioxidant and antiproliferative capacity of Cyperus rotundus products towards K562 erythroleukemia cells. Chem Biol Interact 2009;181:85-94.  Back to cited text no. 301
302.Chiang LC, Cianh W, Chang MY, Ng LT, Lin CC. Antileukemic activity of selected natural products in Taiwan. Am J Chin Med 2003;31:37-46.  Back to cited text no. 302
303.Saleem A, Husheem M, Härkönen P, Pihlaja K. Inhibition of cancer cell growth by crude extract and the phenolics of Terminalia chebula retz. fruit. J Ethnopharmacol 2002;81:327-36.  Back to cited text no. 303
304.Afifi FU, Abu-Dahab R. Phytochemical screening and biological activities of Eminium spiculatum (Blume) Kuntze (family Araceae). Nat Prod Res 2012;26:878-82.  Back to cited text no. 304
305.Hsu HF, Houng JY, Chang CL, Wu CC, Chang FR, Wu YC. Antioxidant activity, cytotoxicity, and DNA information of Glossogyne tenuifolia. J Agric Food Chem 2005;53:6117-25.  Back to cited text no. 305
306.Lin AS, Lin CR, Du YC, Lübken T, Chiang MY, Chen IH, et al. Acasiane A and B and farnesirane A and B, diterpene derivatives from the roots of Acacia farnesiana. Planta Med 2009;75:256-61.  Back to cited text no. 306
307.Wu J, Yi W, Jin L, Hu D, Song B. Antiproliferative and cell apoptosis-inducing activities of compounds from Buddleja davidii in Mgc-803 cells. Cell Div 2012;7:20.  Back to cited text no. 307
308.Xie YY, Yuan D, Yang JY, Wang LH, Wu CF. Cytotoxic activity of flavonoids from the flowers of Chrysanthemum morifolium on human colon cancer Colon205 cells. J Asian Nat Prod Res 2009;11:771-8.  Back to cited text no. 308
309.Lee HJ, Wang CJ, Kuo HC, Chou FP, Jean LF, Tseng TH. Induction apoptosis of luteolin in human hepatoma HepG2 cells involving mitochondria translocation of Bax/Bak and activation of JNK. Toxicol Appl Pharmacol 2005;203:124-31.  Back to cited text no. 309
310.Yoo DR, Jang YH, Jeon YK, Kim JY, Jeon W, Choi YJ, et al. Proteomic identification of anti-cancer proteins in luteolin-treated human hepatoma Huh-7 cells. Cancer Lett 2009;282:48-54.  Back to cited text no. 310
311.Chang J, Hsu Y, Kuo P, Kuo Y, Chiang L, Lin C. Increase of Bax/Bcl-XL ratio and arrest of cell cycle by luteolin in immortalized human hepatoma cell line. Life Sci 2005;76:1883-93.  Back to cited text no. 311
312.Yu J, Liu H, Lei J, Tan W, Hu X, Zou G. Antitumor activity of chloroform fraction of Scutellaria barbata and its active constituents. Phytother Res 2007;21:817-22.  Back to cited text no. 312
313.Zhao Y, Yang G, Ren D, Zhang X, Yin Q, Sun X. Luteolin suppresses growth and migration of human lung cancer cells. Mol Biol Rep 2011;38:1115-9.  Back to cited text no. 313
314.Wang TT, Wang SK, Huang GL, Sun GJ. Luteolin induced-growth inhibition and apoptosis of human esophageal squamous carcinoma cell line Eca109 cells in vitro. Asian Pac J Cancer Prev 2012;13:5455-61.  Back to cited text no. 314
315.Harris DM, Li L, Chen M, Lagunero FT, Go VL, Boros LG. Diverse mechanisms of growth inhibition by luteolin, resveratrol, and quercetin in MIA PaCa-2 cells: A comparative glucose tracer study with the fatty acid synthase inhibitor C75. Metabolomics 2012;8:201-10.  Back to cited text no. 315
316.Luo G, Guan X, Zhou L. Apoptotic effect of citrus fruit extract nobiletin on lung cancer cell line A549 in vitro and in vivo. Cancer Biol Ther 2008;7:966-73.  Back to cited text no. 316
317.Lust S, Vanhoecke B, Van Gele M, Philippé J, Bracke M, Offner F. The flavonoid tangeretin activates the unfolded protein response and synergizes with imatinib in the erythroleukemia cell line K562. Mol Nutr Food Res 2010;54:823-32.  Back to cited text no. 317
318.Huang ST, Wang CY, Yang RC, Chu CJ, Wu HT, Pang JH. Wogonin, an active compound in Scutellaria baicalensis, induces apoptosis and reduces telomerase activity in the HL-60 leukemia cells. Phytomedicine 2010;17:47-54.  Back to cited text no. 318
319.Yu JS, Kim AK. Wogonin induces apoptosis by activation of ERK and p38 MAPKs signaling pathways and generation of reactive oxygen species in human breast cancer cells. Mol Cells 2011;31:327-35.  Back to cited text no. 319
320.Huang KF, Zhang GD, Huang YQ, Diao Y. Wogonin induces apoptosis and down-regulates survivin in human breast cancer MCF-7 cells by modulating PI3K-AKT pathway. Int Immunopharmacol 2012;12:334-41.  Back to cited text no. 320
321.Lee DH, Kim C, Zhang L, Lee YJ. Role of p53, PUMA, and Bax in wogonin-induced apoptosis in human cancer cells. Biochem Pharmacol 2008;75:2020-33.  Back to cited text no. 321
322.Wang W, Guo Q, You Q, Zhang K, Yang Y, Yu J, et al. Involvement of bax/bcl-2 in wogonin-induced apoptosis of human hepatoma cell line SMMC-7721. Anticancer Drugs 2006;17:797-805.  Back to cited text no. 322
323.Cao XD, Ding ZS, Jiang FS, Ding XH, Chen JZ, Chen SH, et al. Antitumor constituents from the leaves of Carya cathayensis. Nat Prod Res 2012;26:2089-94.  Back to cited text no. 323
324.Lee DH, Rhee JG, Lee YJ. Reactive oxygen species up-regulate p53 and Puma; a possible mechanism for apoptosis during combined treatment with TRAIL and wogonin. Br J Pharmacol 2009;157:1189-202.  Back to cited text no. 324
325.Shieh DE, Cheng HY, Yen MH, Chiang LC, Lin CC. Baicalin-induced apoptosis is mediated by Bcl-2-dependent, but not p53-dependent, pathway in human leukemia cell lines. Am J Chin Med 2006;34:245-61.  Back to cited text no. 325
326.Mao W, Chen X, Yang T, Yin Y, Ge M, Luo M, et al. A rapid fluorescent screening method for cellular sensitivity to anti-cancer compound. Cytotechnology 2012;64:451-7.  Back to cited text no. 326


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Acta Histochemica. 2016;
[Pubmed] | [DOI]
25 Polyphenol Composition, Antioxidant Activity and Cytotoxicity of Seeds from Two Underexploited Wild Licania Species: L. rigida and L. tomentosa
Igor Parra Pessoa,José Lopes Neto,Thiago Silva de Almeida,Davi Felipe Farias,Leonardo Vieira,Jackeline Lima de Medeiros,Aline Augusti Boligon,Ad Peijnenburg,Ivan Castelar,Ana Fontenele Urano Carvalho
Molecules. 2016; 21(12): 1755
[Pubmed] | [DOI]
26 Novel Aryl Hydrocarbon Receptor Agonist Suppresses Migration and Invasion of Breast Cancer Cells
Hamza Hanieh,Omar Mohafez,Villianur Ibrahim Hairul-Islam,Abdullah Alzahrani,Mohammad Bani Ismail,Krishnaraj Thirugnanasambantham,Makoto Makishima
PLOS ONE. 2016; 11(12): e0167650
[Pubmed] | [DOI]
27 The potential role of polyphenols in the modulation of skin cell viability by Aspalathus linearis and Cyclopia spp. herbal tea extracts in vitro
Tandeka Unathi Magcwebeba,Sylvia Riedel,Sonja Swanevelder,Pieter Swart,Dalene De Beer,Elizabeth Joubert,Wentzel Christoffel Andreas Gelderblom
Journal of Pharmacy and Pharmacology. 2016; 68(11): 1440
[Pubmed] | [DOI]
28 Anti-proliferative, anti-inflammatory and anti-mutagenic activities of a Prunus mahaleb L. anthocyanin-rich fruit extract
Carmela Gerardi,Stefania Frassinetti,Leonardo Caltavuturo,Antonella Leone,Raffaella Lecci,Nadia Calabriso,Maria Annunziata Carluccio,Federica Blando,Giovanni Mita
Journal of Functional Foods. 2016; 27: 537
[Pubmed] | [DOI]
29 Recent developments in the enzymatic O-glycosylation of flavonoids
Bernd Hofer
Applied Microbiology and Biotechnology. 2016;
[Pubmed] | [DOI]
30 Inhibition of cell proliferation and triggering of apoptosis by agrimonolide through MAP kinase (ERK and p38) pathways in human gastric cancer AGS cells
Hui Teng,Qun Huang,Lei Chen
Food Funct.. 2016; 7(11): 4605
[Pubmed] | [DOI]
31 Chemical Composition, Cytotoxic, Apoptotic and Antioxidant Activities of Main Commercial Essential Oils in Palestine: A Comparative Study
Mohammad A. Al-Tamimi,Bob Rastall,Ibrahim M. Abu-Reidah
Medicines. 2016; 3(4): 27
[Pubmed] | [DOI]
32 Sensitization of K562 Leukemia Cells to Doxorubicin by theViscum albumExtract
Tatjana Srdic-Rajic,Nevena Tisma-Miletic,Milena Cavic,Ksenija Kanjer,Katarina Savikin,Danijel Galun,Aleksandra Konic-Ristic,Tamara Zoranovic
Phytotherapy Research. 2016; 30(3): 485
[Pubmed] | [DOI]
33 One-pot green synthesis of 1,3,5-triarylpentane-1,5-dione and triarylmethane derivatives as a new class of tyrosinase inhibitors
Zong-Ping Zheng,Yi-Nan Zhang,Shuang Zhang,Jie Chen
Bioorganic & Medicinal Chemistry Letters. 2016; 26(3): 795
[Pubmed] | [DOI]
34 Chalcone derivatives cause accumulation of colon cancer cells in the G2/M phase and induce apoptosis
Martin Kello,David Drutovic,Martina Bago Pilatova,Vierka Tischlerova,Pal Perjesi,Jan Mojzis
Life Sciences. 2016; 150: 32
[Pubmed] | [DOI]
35 Electroporation and lipid nanoparticles with cyanine IR-780 and flavonoids as efficient vectors to enhanced drug delivery in colon cancer
Julita Kulbacka,Agata Pucek,Malgorzata Kotulska,Magda Dubinska-Magiera,Joanna Rossowska,Marie-Pierre Rols,Kazimiera Anna Wilk
Bioelectrochemistry. 2016; 110: 19
[Pubmed] | [DOI]
36 Chrysin-piperazine conjugates as antioxidant and anticancer agents
Rahul V. Patel,Riyaz Syed,Anuj K. Rathi,Yoo-Jung Lee,Jung-Suk Sung,Young-Soo Keum
European Journal of Pharmaceutical Sciences. 2016;
[Pubmed] | [DOI]
37 Different concentrations of kaempferol distinctly modulate murine embryonic stem cell function
Marcelo Correia,Ana S. Rodrigues,Tânia Perestrelo,Sandro L. Pereira,Marcelo F. Ribeiro,Maria I. Sousa,João Ramalho-Santos
Food and Chemical Toxicology. 2016; 87: 148
[Pubmed] | [DOI]
38 South Asian Medicinal Compounds as Modulators of Resistance to Chemotherapy and Radiotherapy
N. Prasad,Ganesan Muthusamy,Mohana Shanmugam,Suresh Ambudkar
Cancers. 2016; 8(3): 32
[Pubmed] | [DOI]
39 Troxerutin, a Natural Flavonoid binds to DNA Minor Groove and Enhances Cancer Cell Killing in Response to Radiation
Niranjan A. Panat,Beena G. Singh,Dharmendra K. Maurya,Santosh K. Sandur,Saroj S. Ghaskadbi
Chemico-Biological Interactions. 2016;
[Pubmed] | [DOI]
40 Verbesina encelioides: cytotoxicity, cell cycle arrest, and oxidative DNA damage in human liver cancer (HepG2) cell line
Mai M. Al-Oqail,Maqsood A. Siddiqui,Ebtesam S. Al-Sheddi,Quaiser Saquib,Javed Musarrat,Abdulaziz A. Al-Khedhairy,Nida N. Farshori
BMC Complementary and Alternative Medicine. 2016; 16(1)
[Pubmed] | [DOI]
41 Cancer cell specific cytotoxic effect of Rhoeo discolor extracts and solvent fractions
Rebeca García-Varela,Oscar Raúl Fajardo Ramírez,Sergio O. Serna-Saldivar,Julio Altamirano,Guy A. Cardineau
Journal of Ethnopharmacology. 2016;
[Pubmed] | [DOI]
42 An overview of chemical inhibitors of the Nrf2-ARE signaling pathway and their potential applications in cancer therapy
Jiayu Zhu,Huihui Wang,Feng Chen,Jingqi Fu,Yuanyuan Xu,Yongyong Hou,Henry H. Kou,Cheng Zhai,M. Bud Nelson,Qiang Zhang,Melvin E. Andersen,Jingbo Pi
Free Radical Biology and Medicine. 2016;
[Pubmed] | [DOI]
43 Synthesis,In vitroand Docking Studies of New Flavone Ethers asa-Glucosidase Inhibitors
Syahrul Imran,Muhammad Taha,Nor Hadiani Ismail,Syed Muhammad Kashif,Fazal Rahim,Waqas Jamil,Habibah Wahab,Khalid Mohammed Khan
Chemical Biology & Drug Design. 2016; 87(3): 361
[Pubmed] | [DOI]
44 A pumpless multi-organ-on-a-chip (MOC) combined with a pharmacokinetic-pharmacodynamic (PK-PD) model
Hyuna Lee,Dae Shik Kim,Sang Keun Ha,Inwook Choi,Jong Min Lee,Jong Hwan Sung
Biotechnology and Bioengineering. 2016;
[Pubmed] | [DOI]
45 Evaluation of antioxidant, anti-hemolytic and anticancer activity of various solvent extracts of Acacia hydaspica R. Parker aerial parts
Tayyaba Afsar,Suhail Razak,Muhammad Rashid Khan,Saadia Mawash,Ali Almajwal,Maria Shabir,Ihsan Ul Haq
BMC Complementary and Alternative Medicine. 2016; 16(1)
[Pubmed] | [DOI]
46 Potentiation of luteolin cytotoxicity by flavonols fisetin and quercetin in human chronic lymphocytic leukemia cell lines
Katrin Sak,Kristi Kasemaa,Hele Everaus
Food Funct.. 2016;
[Pubmed] | [DOI]
47 Genetic and epigenetic cancer chemoprevention on molecular targets during multistage carcinogenesis
Hyung Sik Kim,Sam Kacew,Byung Mu Lee
Archives of Toxicology. 2016;
[Pubmed] | [DOI]
48 Parasitic Mistletoes of the Genera Scurrula and Viscum: From Bench to Bedside
Ya Lim,Rajan Rajabalaya,Shirley Lee,Kushan Tennakoon,Quang-Vuong Le,Adi Idris,Ihsan Zulkipli,Natasha Keasberry,Sheba David
Molecules. 2016; 21(8): 1048
[Pubmed] | [DOI]
49 Myricetin Selectively Induces Apoptosis on Cancerous Hepatocytes by Directly Targeting Their Mitochondria
Enayatollah Seydi,Hamid Reza Rasekh,Ahmad Salimi,Zhaleh Mohsenifar,Jalal Pourahmad
Basic & Clinical Pharmacology & Toxicology. 2016; 119(3): 249
[Pubmed] | [DOI]
50 Extraction and purification of total flavonoids from pine needles of Cedrus deodara contribute to anti-tumor in vitro
Xiaofeng Shi,Dongyan Liu,Junmin Zhang,Pengbin Hu,Wei Shen,Bin Fan,Quhuan Ma,Xindi Wang
BMC Complementary and Alternative Medicine. 2016; 16(1)
[Pubmed] | [DOI]
51 In vivo antitumor effect, induction of apoptosis and safety of Remirea maritima Aubl. (Cyperaceae) extracts
Grace Anne A. Dória,Paula P. Menezes,Bruno S. Lima,Bruno S. Vasconcelos,Francilene A. Silva,Raíssa M. Henriques,Marcélia G.D. Melo,Ângela V.F. Alves,Manoel O. Moraes,Cláudia Ó Pessoa,Adriana A. Carvalho,Ana Paula N. Prata,Ricardo Luiz C.A. Junior,Isabel B. Lima-Verde,Lucindo J. Quintans-Júnior,Daniel P. Bezerra,Paulo C.L. Nogueira,Adriano A.S. Araujo
Phytomedicine. 2016;
[Pubmed] | [DOI]
52 Raman microspectroscopy for probing the impact of a dietary antioxidant on human breast cancer cells
P. S. C. Medeiros,A. L. M. Batista de Carvalho,C. Ruano,J. C. Otero,M. P. M. Marques
Food Funct.. 2016;
[Pubmed] | [DOI]
53 Dietary flavonoid fisetin increases abundance of high-molecular-mass hyaluronan conferring resistance to prostate oncogenesis
Rahul K. Lall,Deeba N. Syed,Mohammad Imran Khan,Vaqar M. Adhami,Yuansheng Gong,John A. Lucey,Hasan Mukhtar
Carcinogenesis. 2016; : bgw071
[Pubmed] | [DOI]
54 Tangeretin Alleviates Cisplatin-Induced Acute Hepatic Injury in Rats: Targeting MAPKs and Apoptosis
Hany A. Omar,Wafaa R. Mohamed,Hany H. Arab,El-Shaimaa A. Arafa,Krishnendu Acharya
PLOS ONE. 2016; 11(3): e0151649
[Pubmed] | [DOI]
55 Novel synthesised flavone derivatives provide significant insight into the structural features required for enhanced anti-proliferative activity
Divyashree Ravishankar,Kimberly A. Watson,Francesca Greco,Helen M. I. Osborn
RSC Adv.. 2016; 6(69): 64544
[Pubmed] | [DOI]
56 Flavanone and isoflavone glucosylation by non-Leloir glycosyltransferases
Heike Overwin,Victor Wray,Michael Seeger,Silvia Sepúlveda-Boza,Bernd Hofer
Journal of Biotechnology. 2016; 233: 121
[Pubmed] | [DOI]
57 The Val158Met polymorphism in COMT gene and cancer risk: role of endogenous and exogenous catechols
Katrin Sak
Drug Metabolism Reviews. 2016; : 1
[Pubmed] | [DOI]
58 Molecular mechanisms of action of quercetin in cancer: recent advances
Dharambir Kashyap,Sonam Mittal,Katrin Sak,Paavan Singhal,Hardeep Singh Tuli
Tumor Biology. 2016;
[Pubmed] | [DOI]
59 Selective cytotoxicity of a Vietnamese traditional formula, Nam Dia long, against MCF-7 cells by synergistic effects
My-Nuong Thi Nguyen,Thuy-Duong Ho-Huynh
BMC Complementary and Alternative Medicine. 2016; 16(1)
[Pubmed] | [DOI]
60 Iodine-catalysed regioselective thiolation of flavonoids using sulfonyl hydrazides as sulfenylation reagents
Xia Zhao,Zhijie Deng,Aoqi Wei,Boyang Li,Kui Lu
Org. Biomol. Chem.. 2016;
[Pubmed] | [DOI]
61 Computational predictive models for P-glycoprotein inhibition of in-house chalcone derivatives and drug-bank compounds
Trieu-Du Ngo,Thanh-Dao Tran,Minh-Tri Le,Khac-Minh Thai
Molecular Diversity. 2016;
[Pubmed] | [DOI]
62 Flavonoids from Artemisia sacrorum Ledeb. and their cytotoxic activities against human cancer cell lines
Haidan Yuan,Xuyang Lu,Qianqian Ma,Di Li,Guanghua Xu,Guangchun Piao
Experimental and Therapeutic Medicine. 2016; 12(3): 1873
[Pubmed] | [DOI]
63 Morusin suppresses breast cancer cell growth in vitro and in vivo through C/EBPß and PPAR? mediated lipoapoptosis
Haiyan Li,Qiaoping Wang,Lihua Dong,Chuanlan Liu,Zhen Sun,Ling Gao,Xiujie Wang
Journal of Experimental & Clinical Cancer Research. 2015; 34(1)
[Pubmed] | [DOI]
64 Time-Dependent Metabolism of Luteolin by Human UDP-Glucuronosyltransferases and Its Intestinal First-Pass Glucuronidation in Mice
Lili Wu,Junjin Liu,Weichao Han,Xuefeng Zhou,Xiaoming Yu,Qiang Wei,Shuwen Liu,Lan Tang
Journal of Agricultural and Food Chemistry. 2015; 63(39): 8722
[Pubmed] | [DOI]
65 Benzo(a)pyrene induced lung cancer: Role of dietary phytochemicals in chemoprevention
Eshvendar Reddy Kasala,Lakshmi Narendra Bodduluru,Chandana C. Barua,Chandra Shekhar Sriram,Ranadeep Gogoi
Pharmacological Reports. 2015; 67(5): 996
[Pubmed] | [DOI]
66 Polytrichum commune L.ex Hedw ethyl acetate extract-triggered perturbations in intracellular Ca2+ homeostasis regulates mitochondrial-dependent apoptosis
Wenjuan Yuan,Xiaoxia Cheng,Pan Wang,Yali Jia,Quanhong Liu,Wei Tang,Xiaobing Wang
Journal of Ethnopharmacology. 2015; 172: 410
[Pubmed] | [DOI]
67 Polyphenols, radical scavenger activity, short-chain organic acids and heavy metals of several plants extracts from “Bucharest Delta”
Eugenia Dumitra Teodor,Florentina Gatea,Camelia Albu,Cristina Maria Radulescu,Ana Chira,Gabriel Lucian Radu
Chemical Papers. 2015; 69(12)
[Pubmed] | [DOI]
68 Cell Systems to Investigate the Impact of Polyphenols on Cardiovascular Health
Charlotte Grootaert,Senem Kamiloglu,Esra Capanoglu,John Van Camp
Nutrients. 2015; 7(11): 9229
[Pubmed] | [DOI]
69 Flavonol Regulation in Tumor Cells
Michael A. Lea
Journal of Cellular Biochemistry. 2015; 116(7): 1190
[Pubmed] | [DOI]
70 New Polyphenols Identified in Artemisiae abrotani herba Extract
Elisabeta Baiceanu,Laurian Vlase,Andrei Baiceanu,Madalina Nanes,Dan Rusu,Gianina Crisan
Molecules. 2015; 20(6): 11063
[Pubmed] | [DOI]
71 Induction of NRF2-mediated gene expression by dietary phytochemical flavones apigenin and luteolin
Ximena Paredes-Gonzalez,Francisco Fuentes,Sundrina Jeffery,Constance Lay-Lay Saw,Limin Shu,Zheng-Yuan Su,Ah-Ng Tony Kong
Biopharmaceutics & Drug Disposition. 2015; 36(7): 440
[Pubmed] | [DOI]
72 Chrysin–benzothiazole conjugates as antioxidant and anticancer agents
Bhupendra M. Mistry,Rahul V. Patel,Young-Soo Keum,Doo Hwan Kim
Bioorganic & Medicinal Chemistry Letters. 2015; 25(23): 5561
[Pubmed] | [DOI]
73 Oxidovanadium(IV) complexes with chrysin and silibinin: anticancer activity and mechanisms of action in a human colon adenocarcinoma model
I. E. León,J. F. Cadavid-Vargas,I. Tiscornia,V. Porro,S. Castelli,P. Katkar,A. Desideri,M. Bollati-Fogolin,S. B. Etcheverry
JBIC Journal of Biological Inorganic Chemistry. 2015; 20(7): 1175
[Pubmed] | [DOI]
74 Total synthesis of (±)-Anastatins A and B
Guojun Pan,Yantao Ma,Ke Yang,Xia Zhao,Hui Yang,Qingwei Yao,Kui Lu,Tao Zhu,Peng Yu
Tetrahedron Letters. 2015; 56(30): 4472
[Pubmed] | [DOI]
75 Screening and biological evaluation of myricetin as a multiple target inhibitor insulin, epidermal growth factor, and androgen receptor; in silico and in vitro
Pushpendra Singh,Felix Bast
Investigational New Drugs. 2015; 33(3): 575
[Pubmed] | [DOI]
76 Flavone inhibits nitric oxide synthase (NOS) activity, nitric oxide production and protein S-nitrosylation in breast cancer cells
Wenzhen Zhu,Bingwu Yang,Huiling Fu,Long Ma,Tingting Liu,Rongfei Chai,Zhaodi Zheng,Qunye Zhang,Guorong Li
Biochemical and Biophysical Research Communications. 2015; 458(3): 590
[Pubmed] | [DOI]
77 Administration of a maple syrup extract to mitigate their hepatic inflammation induced by a high-fat diet: a transcriptome analysis
Asuka Kamei,Yuki Watanabe,Fumika Shinozaki,Akihito Yasuoka,Takashi Kondo,Tomoko Ishijima,Tsudoi Toyoda,Soichi Arai,Keiko Abe
Bioscience, Biotechnology, and Biochemistry. 2015; 79(11): 1893
[Pubmed] | [DOI]
78 The in vitro cytotoxic activity of ethno-pharmacological important plants of Darjeeling district of West Bengal against different human cancer cell lines
Bipransh K Tiwary,Sony Bihani,Anoop Kumar,Ranadhir Chakraborty,Runu Ghosh
BMC Complementary and Alternative Medicine. 2015; 15(1): 22
[Pubmed] | [DOI]
79 ERa down-regulation plays a key role in silibinin-induced autophagy and apoptosis in human breast cancer MCF-7 cells
Nan Zheng,Ping Zhang,Huai Huang,Weiwei Liu,Toshihiko Hayashi,Linghe Zang,Ye Zhang,Lu Liu,Mingyu Xia,Shin-ichi Tashiro,Satoshi Onodera,Takashi Ikejima
Journal of Pharmacological Sciences. 2015; 128(3): 97
[Pubmed] | [DOI]
80 Flavonoid glucosylation by non-Leloir glycosyltransferases: formation of multiple derivatives of 3,5,7,3',4'-pentahydroxyflavane stereoisomers
Heike Overwin,Victor Wray,Bernd Hofer
Applied Microbiology and Biotechnology. 2015; 99(22): 9565
[Pubmed] | [DOI]
81 Growth inhibition of luteolin on HepG2 cells is induced via p53 and Fas/Fas-ligand besides the TGF-ß pathway
Su Yee,Hye Choi,Sang Chung,Dong Park,Bokyung Sung,Hae Chung,Nam Kim
International Journal of Oncology. 2015;
[Pubmed] | [DOI]
82 Fisetin and hesperetin induced apoptosis and cell cycle arrest in chronic myeloid leukemia cells accompanied by modulation of cellular signaling
Aysun Adan,Yusuf Baran
Tumor Biology. 2015;
[Pubmed] | [DOI]
83 Mobilization of Copper ions by Flavonoids in Human Peripheral Lymphocytes Leads to Oxidative DNA Breakage: A Structure Activity Study
Hussain Arif,Nida Rehmani,Mohd Farhan,Aamir Ahmad,Sheikh Hadi
International Journal of Molecular Sciences. 2015; 16(11): 26754
[Pubmed] | [DOI]
84 Anticancer potential of selected Fallopia Adans species
Octavian Olaru,Luanne Venables,Maryna van de Venter,George Nitulescu,Denisa Margina,Demetrios Spandidos,Aristidis Tsatsakis
Oncology Letters. 2015;
[Pubmed] | [DOI]
85 Role of the flavonoid-rich fraction in the antioxidant and cytotoxic activities ofBauhinia forficataLink. (Fabaceae) leaves extract
Natalizia Miceli,Luigina Pasqualina Buongiorno,Maria Grazia Celi,Francesco Cacciola,Paola Dugo,Paola Donato,Luigi Mondello,Irene Bonaccorsi,Maria Fernanda Taviano
Natural Product Research. 2015; : 1
[Pubmed] | [DOI]
86 Integration of Quercetin-Iron Complexes into Phosphatidylcholine or Phosphatidylethanolamine Liposomes
Yuri A. Kim,Yury S. Tarahovsky,Elena A. Yagolnik,Svetlana M. Kuznetsova,Eugeny N. Muzafarov
Applied Biochemistry and Biotechnology. 2015; 176(7): 1904
[Pubmed] | [DOI]
87 Flavonoid Fraction ofCitrus ReticulataJuice Reduces Proliferation and Migration of Anaplastic Thyroid Carcinoma Cells
Marilena Celano,Valentina Maggisano,Roberta Francesca De Rose,Stefania Bulotta,Jessica Maiuolo,Michele Navarra,Diego Russo
Nutrition and Cancer. 2015; 67(7): 1183
[Pubmed] | [DOI]
88 Flavones Inhibit the Activity of AKR1B10, a Promising Therapeutic Target for Cancer Treatment
Lucie Zemanova,Jakub Hofman,Eva Novotna,Kamil Musilek,Tereza Lundova,Jana Havrankova,Anna Hostalkova,Jakub Chlebek,Lucie Cahlikova,Vladimír Wsol
Journal of Natural Products. 2015; 78(11): 2666
[Pubmed] | [DOI]
89 Sphingosine Kinase 2 and Ceramide Transport as Key Targets of the Natural Flavonoid Luteolin to Induce Apoptosis in Colon Cancer Cells
Loubna Abdel Hadi,Clara Di Vito,Giovanni Marfia,Anita Ferraretto,Cristina Tringali,Paola Viani,Laura Riboni,Ashley Cowart
PLOS ONE. 2015; 10(11): e0143384
[Pubmed] | [DOI]
90 Derricin and Derricidin Inhibit Wnt/ß-Catenin Signaling and Suppress Colon Cancer Cell Growth In Vitro
Barbara F. Fonseca,Danilo Predes,Debora M. Cerqueira,Alice H. Reis,Nathalia G. Amado,Marina C. L. Cayres,Ricardo M. Kuster,Felipe L. Oliveira,Fabio A. Mendes,Jose G. Abreu,Chunming Liu
PLOS ONE. 2015; 10(3): e0120919
[Pubmed] | [DOI]


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