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 Table of Contents  
REVIEW ARTICLE
Year : 2011  |  Volume : 5  |  Issue : 9  |  Page : 1-12  

Flavonoids: A versatile source of anticancer drugs


Department of Chemistry, University of Rajasthan, Jaipur-302004, Rajasthan, India

Date of Submission18-Jun-2010
Date of Web Publication6-Apr-2011

Correspondence Address:
Neelu Sharma
207, Department of Chemistry, University of Rajasthan, Jaipur-302004, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-7847.79093

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   Abstract 

An exponential increase in the number of studies investigating how different components of the diet interact at the molecular and cellular level to determine the fate of a cell has been witnessed. In search for anticancer drugs compelling data from laboratories, epidemiologic investigations, and human clinical trials showed that flavonoids have important effects on cancer chemoprevention and chemotherapy. In many molecular mechanisms of action for prevention against cancer, flavonoids play a major role by interacting between different types of genes and enzymes. Many mechanisms of action have been identified, including carcinogen inactivation, antiproliferation, cell cycle arrest, induction of apoptosis, inhibition of angiogenesis, antioxidation, and reversal of multidrug resistance or a combination of these mechanisms. This review focuses on the anticancer activity of flavonoids as well as their molecular mechanisms, including the treatment of mammary and prostate cancer. This review also highlights some advanced derivatives of flavonoids, which play an important role against cancer.

Keywords: Apoptosis, estrogens receptor, flavonoids, mammary cancer, prostate cancer


How to cite this article:
Chahar MK, Sharma N, Dobhal MP, Joshi YC. Flavonoids: A versatile source of anticancer drugs. Phcog Rev 2011;5:1-12

How to cite this URL:
Chahar MK, Sharma N, Dobhal MP, Joshi YC. Flavonoids: A versatile source of anticancer drugs. Phcog Rev [serial online] 2011 [cited 2017 May 26];5:1-12. Available from: http://www.phcogrev.com/text.asp?2011/5/9/1/79093


   Introduction Top


More than 8000 different compounds of polyphenols have been known and that can be further divided into 10 different general classes. [1] Flavonoids are part of this family & have more than 4000 varieties. They have been classified according to their molecular structure that consists of two benzene rings joined by a linear three-carbon chain and forms an oxygenated heterocycle (C6-C3-C6) and their large number arises from the various combinations of multiple hydroxyl, methoxyl, and O-glycoside group substituents on the basic benzo--pyrone (C6-C3-C6) [2] moiety.

Flavonoids are one of the common components in the human diet. They are present in foods generally as O-glycosides with sugars bound at C3 position. Average intake of all flavonoids is estimated to be 1 g/day. [3] Phenolic acids, flavonoids, stilbenes, and lignans are the most abundantly occurring polyphenols in plants out of which flavonoids and phenolic acids account for 60% and 30%, respectively, of dietary polyphenols. Major sources of polyphenols are fruits, vegetables, and seeds. Flavonoids are widely present in the genus Citrus (family Rutaceae). [4]

They exhibit properties beneficial for human health because they interact with number of cellular targets, such as anti-oxidant and free-radical scavenger activities also the anti-inflammatory, antiviral, and especially anti-cancer properties. Cancer chemoprevention by use of natural or synthetic substances and its prevention through dietary intervention has become an important issue. It may be controlled by various means, including suppression, blockage, and transformation. Suppressing agents prevent the formation of new cancers from procarcinogens, blocking agents prevent carcinogenic compounds from reaching critical initiation sites, and transformation agents facilitate the metabolism of carcinogenic components into less toxic materials or prevent their biological actions. Flavonoids can act in all the three ways. [5] Many other potential chemopreventive polyphenols may interrupt or reverse the carcinogenesis process. [6]


   Major Molecular Mechanism of Action Top


Polyphenolic compounds display a remarkable spectrum of biological activities, including those that might influence the processes that are dysregulated during cancer development. This includes antiallergic, anti-inflammatory, antioxidant, antimutagenic, anticarcinogenic, and modulation of enzymatic activities. [7],[8],[9] They may therefore have beneficial health effects and can be considered as chemopreventive or therapeutic agents against cancer. [10]

Carcinogenesis is generally considered as a complex and multistep process in which distinct molecular and cellular alterations occur, & to simplify the different possible options for chemoprevention and chemotherapy in cancer development and progression, three stages have been described.

  1. Initiation is a rapid phase, comprises of exposure and interaction of cells, especially DNA, with a carcinogenic agent.
  2. Promotion is relatively lengthy than the previous stage, abnormal cells persist, replicate and may originate a focus of preneoplastic cells.
  3. Progression stage is the final phase of the tumorigenesis that involves the gradual conversion of premalignant cells to neoplastic ones with an increase in invasiveness, metastasis potential, and new blood vessel formation (angiogenesis) [Figure 1].
Figure 1: Three stages of cancer development and progression

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One of the most exciting discoveries is the identification of oncogenes. [11],[12] More than 40 oncogenes have been identified and their protein products have been characterized. These include protein kinases, GTP-binding proteins, and nuclear transcription factors. A unique hypothesis that the activation of transformation might act via protein phosphorylation came into existence. Protein- tyrosine kinases (PTKs) are the group of enzymes that catalyze the transfer of the phosphate of ATP to the hydroxyl group of tyrosine on many key proteins, which in turn induce the cascade of altered cell parameters, a characteristic of transformed cells. [13],[14],[15],[16],[17] This hypothesis has been supported by several recent findings:

1. Activated PTKs have been identified to be the products of approximately half of the known viral transforming genes (oncogenes) [Table 1].
Table 1: Examples of protein-tyrosine kinase gene families

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2. The plasma-membrane receptors for several polypeptide growth factors, such as epidermal growth factor (EGF), transforming growth factor-α (TGF-α), platelet-derived growth factor (PDGF), insulin-like growth factor-1 (IGF-l), macrophage colony stimulating factor-1 (CSF-l), fibroblast growth factors (FGF-1 and FGF-2), nerve growth factor (NGF), and hepatocyte growth factor (HGF) are ligand-activated PTKs [Table 1].

Biomolecular activities of flavonoids

  • Antioxidative effects: inactivation of oxygen radicals
  • Binding of electrophils
  • Induction of protective enzymes: phase 2 with conjugating activities (GT, GST)
  • Apoptosis rate increase
  • Cell proliferation inhibition
  • Lipid peroxidation inhibition
  • Angiogenesis inhibition
  • H-Donation (e.g. GSH-peroxidases)
  • DNA oxidation inhibition

    GST, glutathione S-transferases; GT, glucuronosyl transferases; GSH, glutathione.


The biological properties of citrus flavonoids [5] and the effectiveness of polyphenolics in tea regarding cancer prevention and induction of apoptosis [8] have been widely studied. Flavonols from Brussels sprouts and flavones induce protective enzymes, such as conjugating enzymes, for example, uridine 5'-diphospho (UDP)-GT, GST in gut and liver. [18],[19] These enzymes inactivate electrophils, free radicals, and reactive oxygen species (ROS) and thereby preventing them from becoming mutagens. [20]

[Figure 1] demonstrates the potential mechanisms of inhibition of carcinogenesis by flavonoids & mainly illustrates the inhibitory effects of tea flavonoids on the main biological events that can lead to mutagens and shows how the carcinogenic neoplastic processes (initiation, promotion, and progression) are influenced.

Preventing carcinogen metabolic activation

One of the most important mechanism by which flavonoids can exert their effects is through their interaction with phase I metabolizing enzymes (eg, cytochrome P450), which metabolically activate a large number of procarcinogens to reactivate intermediates that can interact with cellular nucleophiles and ultimately trigger carcinogenesis. Flavonoids inhibit the activities of certain P450 isozymes, such as CYP1A1 and CYP1A2, [21],[22] thus they are likely to have a protective role against the induction of cellular damage by the activation of carcinogens. Another mechanism of action is the induction of phase II metabolizing enzymes (eg, GST, quinone reductase, and UDP-GT) [23],[24] by which carcinogens are detoxified & eliminated from the body. This helps in explaining the chemopreventive effects of flavonoids against carcinogenesis [Figure 2].
Figure 2: Hypothesis of inhibition of carcinogenesis by flavonoids- LOX, Lipoxygenase; COX, Cyclooxygenase; Px, Peroxidase; ROS, Reactive oxygen species; GSH, Glutathione; GST, Glutathione S-transferases; GT, UDP-Glucuronosyl transferases; Px, Peroxidase; NSAID, Nonsteroidal antiinflammatory drugs

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Antiproliferation

The molecular mechanism of antiproliferation may involve the inhibition of the prooxidant process that causes tumor promotion. Growth promoting oxidants and ROS are the major catalysts of the tumor promotion and progression stages. Flavonoids are effective in inhibiting xanthine oxidase, [25] COX or LOX55, [26] and therefore inhibit tumor cell proliferation.

In addition, the mechanism of inhibition of polyamine biosynthesis can contribute to the antiproliferative activities of flavonoids. Ornithine decarboxylase is a rate-limiting enzyme in polyamine biosynthesis & is correlated with the rate of DNA synthesis and cell proliferation in several tissues. Several experiments show that flavonoids can inhibit ornithine decarboxylase induced by tumor promoters causing a subsequent decrease in polyamine and inhibition of DNA and protein synthesis. [27],[28],[29]

Cell cycle arrest

Perturbations in cell cycle progression may account for the anticarcinogenic effects of flavonoids. Due to mitogenic signals, cells enter into a series of regulated steps allowing traverse of the cell cycle, and cyclin-dependent kinases (CDKs) are recognized as key regulators of cell cycle progression. Alteration and deregulation of CDK activity are pathogenic hallmarks of neoplasia. Various types of cancers are associated with hyper activation of CDKs due to mutation of CDK genes or CDK inhibitor genes. Therefore, inhibitors or modulators are of great interest as novel therapeutic agents in cancer. [30],[31] Checkpoints at both G1/S and G2/M of the cell cycle in cultured cancer cell lines have been found to be perturbed by flavonoids, such as silymarin, genistein, quercetin, daidzein, luteolin, kaempferol, apigenin, and epigallocatechin 3-gallate. [32],[33],[34] Studies from various laboratories have revealed that flavopiridol could induce cell cycle arrest during either G1 or G2/M by inhibiting all CDKs. [30],[35]

Induction of apoptosis

The significant anticancer properties observed in flavonoids may be due to frank apoptosis. [36],[37],[38],[39] Apoptosis is an active form of cell death that plays an essential role in the development and survival by eliminating damaged or unwanted cells. It is tightly regulated by a set of genes that promote apoptosis cell survival and is mediated through a highly organized network of interacting protease and their inhibitors in response to noxious stimuli from either inside or outside of the cell. Dysregulation of apoptosis plays a critical role in oncogenesis. Flavonoids have shown to induce apoptosis in some cancer cell lines, while sparing normal cells. The molecular mechanisms by which flavonoids induce apoptosis have not been clarified. Several mechanisms may be involved, including inhibition of DNA topoisomerase I/II activity, [40],[41],[42] decrease of ROS, [43] regulation of heat shock protein expression, [44] modulation of signaling pathways, [37] downregulation of nuclear transcription factor kappa B (NF-κB), activation of endonuclease, and suppression of Mcl-1 protein. [38],[43],[45],[46]

In vitro studies of flavonoids

In vitro , flavonoids modify the activity of enzymatic systems in mammals (eg, kinases, phospholipases, ATPase, lipooxygenases, cyclooxygenases, and phosphodiesterases). A correlation has been observed in some cases between the flavonoid structure and its enzymatic activity. [47],[48],[49],[50],[51] Much of these effects can be attributed to the abilities of flavonoids to interact with the nucleotide binding sites of regulatory enzymes.

Many researchers have conducted in vitro studies on the potential anticancer activity of flavonoids in diverse cell systems. The report on the inhibitory properties of flavonoids against carcinogenesis are summarized in [Table 2]. Hirano and co-workers examined anticancer efficacy of 28 flavonoids on human acute myeloid leukemia cell line HL-60 and differences between antiproliferative activity and cytotoxicity of these compounds with those of four clinical anticancer agents. Out of 28 flavonoids, 8 showed considerable suppressive effects on HL-60 cell growth with IC 50 s ranging from 10-940 ng/mL. Among these compounds, genistein, honokiol, machilin A, matairesinol, and arctigenin had the strongest effects with IC 50 s less than 100 ng/ml, which were almost equivalent to the effects of current anti-cancer agents. The flavonoid genistein and the lignans, however, showed little or no cytotoxicity against HL-60 cells as assessed by dye exclusion tests (LC 50 s>2,900ng/ml), whereas the regular anti-cancer agents had potent cytotoxicity [52],[53] and more than 30 flavonoids were screened for their effects on cell proliferation and potential cytotoxicity in human colon cancer cell lines Caco-2 and HT-29. There was no obvious structure activity relationship in the antiproliferative effects either on the basis of sub-classes with respect to type or position of substituents within a class. [53]
Table 2: Anticancer activities of flavonoids in various cancer cell lines


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Flavonoids showed inhibition of carcinogenesis in vitro but substantial evidences indicate that they can also do so in vivo.[72],[73] Studies on animals and investigations using different cellular models suggest that certain flavonoids could inhibit tumor initiation as well as tumor progression. [27],[28],[29],[74] Siess and co-workers investigated the effects of feeding rats with flavone, flavanone, tangeretin, and quercetin on two steps of aflatoxin B1(AFB1)-induced hepatocarcinogenesis (initiation and promotion) and found that flavone, flavanone, and tangeretin administered through the initiation period, decreased the number of γ-glutamyl transpeptidase-preneoplastic foci. Therefore flavanone acts as an anti-initiator as well as an anti-promoter. [75] Lung tumorigenesis is prevented by catechin enriched tea and is demonstrated in A/J mice. [76] Two weeks before the 4-(methylnitrosamine)-1-(3-pyridyl)-1 butanone (NNK) treatment, decaffeinated green or black tea is given to mice for 3 or 15 weeks. This markedly reduced the number of tumors formed in the mice. In those mice adenomas have developed at 16 weeks after the NNK injection; and, the progression of adenomas to adenocarcinomas was significantly inhibited by administration of black tea. These experiments infer that tea has broad inhibitory activity against lung carcinogenesis and it is effective when administered during the initiation, promotion, or progression stages of carcinogenesis. Moreover, there is evidence for the suppression of tumor invasion and metastasis by flavonoids.

Catechins, a group of flavonoid molecules, in vitro[77] inhibit the invasion of mouse MO4 cells into embryonic chick heart fragments. A polymethoxy flavonoid, nobiletin from Citrus depressa inhibits the tumor invasion activity of human fibrosarcoma HT-108 cells in the Matrigel model, by the suppression of expression of matrix metalloproteases (MMPs) and augmenting of tissue inhibitors of metalloproteinases. [78] Quercetin and apigenin inhibited melanoma cell (B16-BL6) growth and metastatic potential in syngenetic mice, in vitro.[60] They were found to significantly decrease the invasion of B16-BL6 cells. Also apigenin significantly decreased the invasion of lymphatic vessel of intestinal adenocarcinomas that are induced by azoxymethane and are of cancer peritoneal metastasis, enhanced by bombesin in male Wistar rats. The inhibitory effect of apigenin on cancer metastasis may be through the inhibition of phosphorylation of mitogen-activated protein kinase (MAPK). [79]


   Treatment of Different Types of Cancer by Flavonoids Top


In Western countries, breast cancer is one of the most common causes of death in women and prostate cancer is the second most common cause of death in men. In China, Japan, and other Asian countries, where diets include relatively high concentrations of soy isoflavones, death due to cancer is comparatively rare. [80]

Phytoestrogens are plant-derived chemicals that bind to the estrogen receptor (ER) and induce various estrogenic and antiestrogenic responses. [81] The extensively studied class of phytoestrogens are the isoflavones. High concentrations of the isoflavones genistein and diadzein are present in legumes and ingestion of these substances may reduce the risk of cancer, particularly in the breast and prostate.

Experimentally, thoroughly studied soy isoflavone is genistein. It is clear, however, that in vitro micromolar concentrations of genistein can inhibit the growth of a wide variety of cancer cells. [81] In ER-positive cells, growth inhibitors compete with estradiol for receptor binding, and translocation of the hormone-receptor complex takes place in the nucleus and ultimately, reduce the stimulation of a variety of downstream effects. [82]

Soy containing isoflavones are among the most versatile biopharmaceuticals known. Genistein, daidzein, and glycitein are the main isoflavones found in soy foods [Figure 3]. Isoflavones, one of the major class of phytoestrogens, are structurally similar to estrogens, [83] binds to ERs, and hence have estrogenic and anti-estrogenic activities and their own growth-inhibitory effects are independent of ER. [84],[85] Isoflavones and their metabolites are considered to reduce the risk of cancer and to have potent anticarcinogenic activities [81],[86] by direct inhibition of PTK, [87] inhibition of DNA-topoisomerase II, [88] inhibition of angiogenesis, [89] antiproliferation, and cell cycle arrest, [90] and induction of apoptosis. [91]
Figure 3: Some of the isoflavones found in soy foods

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Two major types of cancer and their treatment using flavonoids are discussed in the following sections.


   Mammary Tumor Top


Evidences support that estrogens are involved in mammary carcinomas. Researchers have found that in ER-positive and ER-negative mammary cell lines of women affected with breast cancer, the tumor-suppressing gene pRb2/p13 binds to a specific region on the ER gene alpha and forms molecular complexes recruiting and interacting with several proteins. They discovered that ER-negative cells that are able to silent the expression of the ER pRb2/p13 form a specific molecular complex recruiting a different sequence of proteins than in the ER-positive cells. Our hypothesis is that the sequence of epigenetic events for establishing and maintaining a silence state of ER gene alpha during the breast cancer progression is mediated by pRb2/p13 in association with specific proteins that modify the DNA structure through specific mechanisms. [92]

Estradiol, the most potent endogenous estrogen, is biosynthesized from androgens by cytochrome P450 enzyme complex called aromatase. Some flavonoids have been reported as potent aromatase inhibitors. [93],[94],[95] Therefore, flavonoids are considered as potential agents against breast cancer by inhibiting aromatase activity.

Investigation of seven metabolites of isoflavones for their growth-inhibitory effects and later compared with the isoflavones genistein, daidzein, and glycitein present on human breast cancer MCF-7 and MDA-MB- 468 cells. The novel metabolite 2-de-O-DMA exhibited a potent growth inhibitory effect on human breast ER-positive MCF-7 cells and ER-negative MDA-MB-468 cells. This metabolite was further examined on other human breast cancer SK-BR-3 (ER-negative), human breast noncancer MCF-10A (ER-negative), human prostate cancer LNCaP [androgen receptor (AR)-positive], and DU145 (AR-negative) cell lines. Hence this study shows that the novel metabolite 2-de-O-DMA is still able to inhibit the proliferation of MCF-10A (ER-negative), SK-BR-3 (ER-negative), LNCaP, and DU145 cells. [84],[85],[86],[87],[88],[89],[90],[91]

Epidemiologic studies have showed that populations with high isoflavone intake through soy consumption have low rates of breast, prostate, and colon cancer. The isoflavone polyphenol genistein in soybean is considered to be a potent chemopreventive agent against cancer. [96]


   Prostate Cancer Top


Prostate cancer (PCA) is considered as one of the major concerns in the field of cancer therapy. PCA is an aging disease and oxidative stress & is a major factor in the promotion/progression of malignancy. [97] Furthermore, activation of many kinases involved in NF-κB pathway is dependent on oxidative stress. [98],[99] ROS cause prolonged NF-κB DNA binding activity and antioxidants have shown to diminish this activity. [100] Based on the above study, one approach to control PCA growth and progression can be inhibition of constitutive NF-κB activation, however, limited efforts have been made in this direction. Some flavonoids play an important role in preventing PCA by various modes of action.

Silibinin is a flavonolignan present in milk thistle seeds. It is a promising chemopreventive agent against human PCA without showing any apparent toxic side effects. [101] Silibinin has shown strong anticancer efficacy against both androgen-dependent and -independent advanced human PCA cells. [102],[103] Silibinin inhibits TGF expression-, secretion, and down-regulates EGFR-Erk1/2 activation in both LNCaP and DU145 cells, which contributes to the growth inhibitory effects in these cell lines. [103]

Recently, at pharmacologically achievable silibinin concentrations (0.02-20 μM) observed increased insulin-like growth factor-binding protein 3 (IGFBP-3) accumulation in PC-3 cell conditioned medium and a dose-dependent increase of IGFBP-3 mRNA abundance with a 9-fold increase over baseline at 20 μM silibinin. [104] Silibinin also showed, effect on membrane signaling related to erbB1 activation in human PCA LNCaP and DU145 cells. [105] Activation of NF-κB by cytokines is mediated by signal transduction cascades, leading to activation of the IκB kinases, IKKα and IKKβ. Silibinin inhibited the constitutive activation of NF-κB and IKKα in PC-3 and DU-145 cells, and blocked stimulated activation of NF-κB in LNCaP cells. [106] Lastly, the results clearly indicate that silibinin effectively sensitizes DU145 cells to cisplatin- and carboplatin-induced growth inhibition and apoptosis, possibly via an increase in G2M arrest suggesting that studies done in vivo are needed in pre-clinical PCA models of such combinations, which might provide scientific base in developing more effective treatment against human PCA.

Luteolin (30, 40, 5,7-tetrahydroxyflavone) has an antiproliferation property that acts via arresting cell cycle and apoptosis in many human cancer cells, including PCA cells. [107],[108] Studies showed that luteolin inhibits the expression of AR and growth in LNCaP human PCA cells and xenografted mice. The reduction in AR levels by luteolin involve a transcriptional or post translational mechanism. Moreover, it suggests that luteolin suppresses the association between AR and heat-shock protein 9(hsp90) and induces AR protein degradation through a proteasome-mediated pathway. [109] These results indicate that AR is critical for PCA cell growth and survival and that it is a potential molecular target for luteolin-mediated anticancer therapy.

Quercetin exerts the strongest expression of MMP-2 and -9 through the inhibition of protein kinases. Quercetin inhibits the secretion of MMP-2 also in tumor cells and thereby reduces the potential for metastasis. [110],[111],[112] Quercetin also acts as a preventive agent against cancer invasion. By targeting specific genes that regulate the expression of MMPs can be advantageous in the treatment of PCA.

Nutritional science contributes substantially also. Identification of biomarkers plays an important role in this effort through the use of new and emerging technologies. At the same time, gene expression profiling and proteomics provide novel insights into cancer-related traits. Early detection is the desired strategy for reducing cancer-related morbidity and mortality, and collaborative effort between academic and industry leaders brings expert solutions for cancer.


   Advanced Development of Anticancer Agent from Natural Flavonoids Top


In the search for anticancer drugs from botanical sources, plant extracts were fractionated by various means and were then in vitro tested for anticancer properties. Here, we discuss flavonoid compounds that display their anticancer activity in recent time, including those that are able to influence processes that are dysregulated during cancer development.

(a) Flavone 8-acetic acid (FAA) represents a novel chemical structure undergoing clinical trials as an anticancer drug. Most unusual property of FAA is its ability to reduce tumour blood flow dramatically, which may provide the appropriate conditions for reactive chemistry to occur which distinguish it from a conventional cytotoxic compound, particularly in the response of solid murine tumors. [113] Its clinical use has a number of pharmacologic drawbacks, including low dose potency and dose-dependent pharmacokinetics. So in search for better analogs of FAA-, several derivatives of FAA were synthesized that showed potent antitumor effect, such as xanthenone-4-acetic acid (XAA) and its 5,6-dimethyl derivative (5,6-MeXAA) that displayed very effective pharmacokinetic properties. [114],[115] 5,6-MeXAA ( NSC 640488) was 14-fold more potent than the investigational chemotherapeutic drug flavone-8-acetic acid (NSC 347512) in stimulating tumouricidal activity in cultures of resident murine peritoneal macrophages. [116] 5,6-MeXAA, an another derivative of FAA is a small molecule of flavonoid class that has an antitumor activity due to its ability to induce high local levels of tumor necrosis factor (TNF) that disrupts established blood vessels within tumors. [117],[118] 5,6-MeXAA and FAA have shown potential antitumour activity in several bioreductive drugs by inhibiting enzyme DT-diaphorase (NAD(P)-H Quinone oxidoreductase EC 1.6.99.2) with respect to NADH, Ki values of 75 and 20 μM, respectively. [l18],[119] Also fluorine derivative of FAA bearing a fluorine atom at the 7th position is a most active compound showing remarkable activities in murine cells, but not confirmed in human models. [120]

(b) Flavopiridol, the first CDK inhibitor tested on human, demonstrated clear effects on cell cycle progression, induced differentiation, and apoptosis depending on the relation between transcription factor E2F1 and RB. [121],[122] Flavopiridol undergoes Phase II single-agent trials and Phase I combination trials (with paclitaxel and cisplatin). The drug showed in vivo antitumor activity against a variety of tumor xenografts. [123],[124]

(c) A new flavone glycoside, chrysoeriol 7-O-(2''-O-6'''-O-acetyl-β-D-glucopyranosyl-β-D-glucopyranoside (1), along with 14 known compounds (2-15) was isolated from Carduus crispus Linn. plant. The antitumor activity of compound (1), (4) and (5) was also tested. [125]

(d) Nobiletin (5, 6, 7, 8, 3'',4''-hexamethoxyflavone)-, a citrus flavonoid-, extracted from Citrus depressa Hayata, was examined for its antitumor activity on human gastric cancer cell lines. Cell-cycle analysis revealed that nobiletin acted on these cells through several ways, namely, by direct cytotoxicity, induction of apoptosis, and modulation of cell cycle. [126]

(e) The flavonoid silybin and its bioavailable derivative IdB 1016 (silipide) enhance the antitumor activity of cisplatin (CDDP), the most commonly used drug in the treatment of gynecologic malignancies [Figure 4]. [127]
Figure 4: Chemical structure of advanced anticancerous flavonoids

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(f) Natural flavone diosmetin showed inhibition of proliferation of breast adenocarcinoma MDA-MB 468 and normal breast MCF-10A cells and was found that this compound is selective for the cancer cells with slight toxicity in the normal breast cells. [128]

(g) Quercetin 3-O-amino acid-esters, a new type of quercetin derivatives have been successfully prepared for the first time. Different from quercetin, the novel compounds show higher selectivity as inhibitors against Src tyrosine kinase (IC 50 ) than against EGFR tyrosine kinase. [129]

(h) The modified derivative of flavone, such as trans-bis-(3-aminoflavone-kappa2 N,-O)bis (perchlorato kappa O) copper(II), showed potential antitumor properties. [130]

(i) Myricetin-3-O-(L-rhamnopyranoside and quercetin-3-O-lactopyranoside isolated from Byrsonima crassa, Davilla elliptica, and Mouriri showed antitumor and anti-inflammatory activities. [131]

In the past, many attempts have been made to obtain anticancerous plant originated flavonoids and the efforts will further be continued until a satisfactory treatment becomes available. In this regard, a number of medicinal plants having anticonvulsant potential are reviewed.

 
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[Pubmed] | [DOI]
5 Understanding the Effectiveness of Natural Compound Mixtures in Cancer through Their Molecular Mode of Action
Thazin Aung,Zhipeng Qu,R. Kortschak,David Adelson
International Journal of Molecular Sciences. 2017; 18(3): 656
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6 Anticancer potential of Thevetia peruviana fruit methanolic extract
Alberto Ramos-Silva,Faviola Tavares-Carreón,Mario Figueroa,Susana De la Torre-Zavala,Argel Gastelum-Arellanez,Aída Rodríguez-García,Luis J. Galán-Wong,Hamlet Avilés-Arnaut
BMC Complementary and Alternative Medicine. 2017; 17(1)
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7 Inhibitory effects of the dietary flavonoid quercetin on the enzyme activity of zinc(II)-dependent yeast alcohol dehydrogenase: Spectroscopic and molecular docking studies
Sutanwi Bhuiya,Lucy Haque,Ankur Bikash Pradhan,Suman Das
International Journal of Biological Macromolecules. 2017; 95: 177
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8 One-pot synthesis of novel fused pentacyclic chromenopyrimidobenzimidazolones and benzimidazolyl-chromenyl-substituted thiazolidinones
Nicolaos M. Drosos,Chrisoula Kakoulidou,Marianna Raftopoulou,Julia Stephanidou-Stephanatou,Constantinos A. Tsoleridis,Antonis G. Hatzidimitriou
Tetrahedron. 2017; 73(1): 1
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9 Intramolecular hydrogen bonding in myricetin and myricitrin. Quantum chemical calculations and vibrational spectroscopy
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Journal of Molecular Structure. 2017; 1131: 242
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10 Quercetin derivatives as potent inducers of selective cytotoxicity in glioma cells
Paola DellæAlbani,Barbara Di Marco,Sonia Grasso,Concetta Rocco,Mario C. Foti
European Journal of Pharmaceutical Sciences. 2017;
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11 Use of multiresponse statistical techniques to optimize the separation of diosmin, hesperidin, diosmetin and hesperitin in different pharmaceutical preparations by high performance liquid chromatography with UV-DAD
Mohamad Subhi Sammani,Sabrina Clavijo,Lindomar Portugal,Ruth Suárez,Hassan Seddik,Víctor Cerdà
Talanta. 2017;
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12 Sea Buckthorn Leaf Extract Inhibits Glioma Cell Growth by Reducing Reactive Oxygen Species and Promoting Apoptosis
Sung-Jo Kim,Eunmi Hwang,Sun Shin Yi,Ki Duk Song,Hak-Kyo Lee,Tae-Hwe Heo,Sang-Kyu Park,Yun Joo Jung,Hyun Sik Jun
Applied Biochemistry and Biotechnology. 2017;
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13 Metabolic Profile and Root Development of Hypericum perforatum L. In vitro Roots under Stress Conditions Due to Chitosan Treatment and Culture Time
Elisa Brasili,Alfredo Miccheli,Federico Marini,Giulia Praticò,Fabio Sciubba,Maria E. Di Cocco,Valdir Filho Cechinel,Noemi Tocci,Alessio Valletta,Gabriella Pasqua
Frontiers in Plant Science. 2016; 7
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14 Screening dietary flavonoids for the reversal of P-glycoprotein-mediated multidrug resistance in cancer
S. Mohana,M. Ganesan,B. Agilan,R. Karthikeyan,G. Srithar,R. Beaulah Mary,D. Ananthakrishnan,D. Velmurugan,N. Rajendra Prasad,Suresh V. Ambudkar
Mol. BioSyst.. 2016;
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15 Evaluation of Synergistic Interactions on Antioxidant and Anticancer Efficacy of Methanol Extracts of some Egyptian Spices in Combination
Amr F. Mansour,Manal M. Ramadan,Reda M. Fekry,Marwa T. Salem,Ayman A. Mohammad,Mamdouh M. Ali,Noha S. Mohammed
International Journal of Biological Chemistry. 2016; 11(1): 9
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16 Bioassay-guided separation and identification of anticancer compounds in Tagetes erecta L. flowers
Hong Lu,Shanshan Yang,Hong Ma,Zhao Han,Yaozhou Zhang
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17 The G Protein GasActs as a Tumor Suppressor in Sonic Hedgehog Signaling-driven Tumorigenesis
Rohit Rao,Ralph Salloum,Mei Xin,Q. Richard Lu
Cell Cycle. 2016; : 00
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18 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;
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19 Modulation of intracellular expression of IFN? and IL-2 in culture of splenic T lymphocytes by some flavonoid glycosides ofAlchornea floribunda
Festus B. C. Okoye,Damian Chukwu Odimegwu,Chukwuemeka Sylvester Nworu,Matthias Onyebuchi Agbo,Charles Okechukwu Esimone,Patience Ogoamaka Osadebe,Peter Proksch
Pharmaceutical Biology. 2016; : 1
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20 Anti-angiogenic effect of ALS-L1023, an extract ofMelissa officinalisL., on experimental choroidal neovascularization in mice
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Clinical & Experimental Ophthalmology. 2016; 44(1): 43
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21 Eupalitin induces apoptosis in prostate carcinoma cells through ROS generation and increase of caspase-3 activity
Sarjeel Kaleem,Sahabjada Siddiqui,Hefazat Hussain Siddiqui,Hefazat Hussain Badruddeen,Arshad Hussain,Mohammad Arshad,Juber Akhtar,Aleza Rizvi
Cell Biology International. 2016; 40(2): 196
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22 Anti-inflammatory and antioxidant activity of polyphenolic extracts fromLactuca sativa(var.Maravilla de Verano) under different farming methods
Simona Adesso,Giacomo Pepe,Eduardo Sommella,Michele Manfra,Antonio Scopa,Adriano Sofo,Gian Carlo Tenore,Mariateresa Russo,Francesca Di Gaudio,Giuseppina Autore,Pietro Campiglia,Stefania Marzocco
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23 The in vivo antineoplastic and therapeutic efficacy of troxerutin on rat preneoplastic liver: biochemical, histological and cellular aspects
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24 Liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) based bioavailability determination of the major classes of phytochemicals
Evgenios Stylos,Maria V. Chatziathanasiadou,Aggeliki Syriopoulou,Andreas G. Tzakos
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25 Regioselective ortho-hydroxylations of flavonoids by yeast
Sandra Sordon,Anna Madej,Jaroslaw Poplonski,Agnieszka Bartmanska,Tomasz Tronina,Ewa Brzezowska,Piotr Juszczyk,Ewa Huszcza
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26 Cell cycle and apoptosis pathway modulation by Tualang honey in ER-dependent and -independent breast cancer cell lines
Agustine Nengsih Fauzi,Nik Soriani Yaacob
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27 Functional Components of Carob Fruit: Linking the Chemical and Biological Space
Vlasios Goulas,Evgenios Stylos,Maria Chatziathanasiadou,Thomas Mavromoustakos,Andreas Tzakos
International Journal of Molecular Sciences. 2016; 17(11): 1875
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28 Flavonoids from Heliotropium subulatum exudate and their evaluation for antioxidant, antineoplastic and cytotoxic activities II
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29 A New Kaempferol-based Ru(II) Coordination Complex, Ru(kaem)Cl(DMSO)3 : Structure and Absorption-Emission Spectroscopy Study
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30 Evaluation of “Dream Herb,”Calea zacatechichi, for Nephrotoxicity Using Human Kidney Proximal Tubule Cells
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31 Biophysical insight into the interaction of the bioflavonoid kaempferol with triple and double helical RNA and the dual fluorescence behaviour of kaempferol
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32 Bioactive Formylated Flavonoids fromEugenia rigida: Isolation, Synthesis, and X-ray Crystallography
Mohamed A. Zaki,N. P. Dhammika Nanayakkara,Mona H. Hetta,Melissa R. Jacob,Shabana I. Khan,Rabab Mohammed,Mohamed A. Ibrahim,Volodymyr Samoylenko,Christina Coleman,Frank R. Fronczek,Daneel Ferreira,Ilias Muhammad
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33 In vitroeffects of some flavonoids and phenolic acids on human pyruvate kinase isoenzyme M2
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34 Zapotin (5,6,2',6'-tetramethoxyflavone) modulates the crosstalk between autophagy and apoptosis pathways in cancer cells with overexpressed constitutively active PKC?
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35 Application of Hydrophilic Interaction Liquid Chromatography for the Quantification of Flavonoids inGenista tinctoriaExtract
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36 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
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37 Hesperetin and Naringenin sensitize HER2 positive cancer cells to death by serving as HER2 Tyrosine Kinase inhibitors
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38 Polyalkoxyflavonoids as inhibitors of cell division
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39 Clinacanthus nutans (Burm. f.) Lindau Ethanol Extract Inhibits Hepatoma in Mice through Upregulation of the Immune Response
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40 Chemical Characterization and in Vitro Cytotoxicity on Squamous Cell Carcinoma Cells of Carica Papaya Leaf Extracts
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41 Hesperidin: A promising anticancer agent from nature
Kasi Pandima Devi,T. Rajavel,Seyed Fazel Nabavi,William N. Setzer,Amirhossein Ahmadi,Kowsar Mansouri,Seyed Mohammad Nabavi
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42 Myricetin induces apoptosis by inhibiting P21 activated kinase 1 (PAK1) signaling cascade in hepatocellular carcinoma
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43 Synthesis and anticancer activities of 3-arylflavone-8-acetic acid derivatives
Guang-Hua Yan,Xiao-Fang Li,Bing-Chen Ge,Xiu-Dong Shi,Yu-Fang Chen,Xue-Mei Yang,Jiang-Ping Xu,Shu-Wen Liu,Pei-Liang Zhao,Zhong-Zhen Zhou,Chun-Qiong Zhou,Wen-Hua Chen
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44 Linking Flavonoids to Gold - A New Family of Gold Compounds for Potential Therapeutic Applications
Nedaossadat Mirzadeh,Steven H. Privér,Amanda Abraham,Ravi Shukla,Vipul Bansal,Suresh K. Bhargava
European Journal of Inorganic Chemistry. 2015; 2015(25): 4275
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45 Anti-diabetic potential of Urena lobata leaf extract through inhibition of dipeptidyl peptidase IV activity
Yudi Purnomo,Djoko Wahono Soeatmadji,Sutiman Bambang Sumitro,Mochamad Aris Widodo
Asian Pacific Journal of Tropical Biomedicine. 2015; 5(8): 645
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46 A Network Flow Approach to Predict Protein Targets and Flavonoid Backbones to Treat Respiratory Syncytial Virus Infection
José Eduardo Vargas,Renato Puga,Joice de Faria Poloni,Luis Fernando Saraiva Macedo Timmers,Barbara Nery Porto,Osmar Norberto de Souza,Diego Bonatto,Paulo Márcio Condessa Pitrez,Renato Tetelbom Stein
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47 Chemical composition and in vitro antioxidant and antitumor activities of Eucalyptus camaldulensis Dehn. leaves
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48 Inhibition of Staphylococcus aureus PriA Helicase by Flavonol Kaempferol
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49 Synthesis of Polyamidoamine Dendrimer for Encapsulating Tetramethylscutellarein for Potential Bioactivity Enhancement
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50 Phytochemical-mediated Protein Expression Profiling and the Potential Applications in Therapeutic Drug Target Identifications
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51 Growth inhibition of luteolin on HepG2 cells is induced via p53 and Fas/Fas-ligand besides the TGF-ß pathway
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52 Naringin induces autophagy-mediated growth inhibition by downregulating the PI3K/Akt/mTOR cascade via activation of MAPK pathways in AGS cancer cells
Suchismita Raha,Silvia Yumnam,Gyeong Hong,Ho Lee,Venu Saralamma,Hyeon-Soo Park,Jeong Heo,Sang Lee,Eun Kim,Jin-A Kim,Gon Kim
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53 Synthesis, characterization, anti-inflammatory and anti-proliferative activity against MCF-7 cells of O-alkyl and O-acyl flavonoid derivatives
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54 Effect of pH on the chemical modification of quercetin and structurally related flavonoids characterized by optical (UV-visible and Raman) spectroscopy
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55 Salicylic acid treatment enhances expression of chalcone isomerase gene and accumulation of corresponding flavonoids during fruit maturation of Lycium chinense
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European Food Research and Technology. 2014; 239(5): 857
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56 Isomerization and redox tuning in ‘Maya yellow’ hybrids from flavonoid dyes plus palygorskite and kaolinite clays
Antonio Doménech-Carbó,María Teresa Doménech-Carbó,Laura Osete-Cortina,Francisco M. Valle-Algarra,David Buti
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57 Computational insight of the mechanism of Algar–Flynn–Oyamada (AFO) reaction
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58 Chromeno[2,3-c]pyrroles by one-pot multicomponent domino addition–amination reaction
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59 The G protein a subunit Gas is a tumor suppressor in Sonic hedgehog-driven medulloblastoma
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60 Polyphenol contents of five of medicinal plants from Cameroon and effects of their extracts on antioxidant capacities of human breast cancer cells
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61 Targeting the Achilles Heel of Multidrug-Resistant Cancer by Exploiting the Fitness Cost of Resistance
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62 Apoptotic effects of 7,8-dihydroxyflavone in human oral squamous cancer cells through suppression of Sp1
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63 Collateral sensitivity of resistant MRP1-overexpressing cells to flavonoids and derivatives through GSH efflux
Doriane Lorendeau,Lauriane Dury,Estelle Genoux-Bastide,Florine Lecerf-Schmidt,Claudia Simões-Pires,Pierre-Alain Carrupt,Raphaël Terreux,Sandrine Magnard,Attilio Di Pietro,Ahcène Boumendjel,Hélène Baubichon-Cortay
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64 Saffron and natural carotenoids: Biochemical activities and anti-tumor effects
Azam Bolhassani,Afshin Khavari,S. Zahra Bathaie
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65 Enhanced transdermal delivery of luteolin via non-ionic surfactant-based vesicle: quality evaluation and anti-arthritic assessment
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66 Centipedegrass extract induces apoptosis through the activation of caspases and the downregulation of PI3K/Akt and MAPK phosphorylation in leukemia cells
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67 Anticancer Properties of Teucrium persicum in PC-3 Prostate Cancer Cells
Majid Tafrihi,Samane Toosi,Tayebeh Minaei,Ahmad Reza Gohari,Vahid Niknam,Seyed Mahmoud Arab Najafi
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68 Effects of Crude Extracts from Medicinal HerbsRhazya strictaandZingiber officinaleon Growth and Proliferation of Human Brain Cancer Cell LineIn Vitro
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69 Analysis of the erythroid differentiation effect of flavonoid apigenin on K562 human chronic leukemia cells
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Chemico-Biological Interactions. 2014; 220: 269
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70 Isoliquiritigenin, a flavonoid from licorice, blocks M2 macrophage polarization in colitis-associated tumorigenesis through downregulating PGE2 and IL-6
Haixia Zhao,Xinhua Zhang,Xuewei Chen,Ying Li,Zunqiong Ke,Tian Tang,Hongyan Chai,Austin M. Guo,Honglei Chen,Jing Yang
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71 Deglycosylation of isoflavoneC-glycosides by newly isolated human intestinal bacteria
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72 Flavonoid Apigenin Inhibits Lipopolysaccharide-Induced Inflammatory Response through Multiple Mechanisms in Macrophages
Xiaoxuan Zhang,Guangji Wang,Emily C. Gurley,Huiping Zhou,Mengwei Zang
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73 Chromones as a privileged scaffold in drug discovery: A review
Rangappa S. Keri,Srinivasa Budagumpi,Ranjith Krishna Pai,R. Geetha Balakrishna
European Journal of Medicinal Chemistry. 2014; 78: 340
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74 UHPLC profiling and effects on LPS-stimulated J774A.1 macrophages of flavonoids from bergamot (Citrus bergamia) juice, an underestimated waste product with high anti-inflammatory potential
Eduardo Sommella,Giacomo Pepe,Francesco Pagano,Gian Carlo Tenore,Stefania Marzocco,Michele Manfra,Giorgio Calabrese,Rita Patrizia Aquino,Pietro Campiglia
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75 A Generic Multiple Reaction Monitoring Based Approach for Plant Flavonoids Profiling Using a Triple Quadrupole Linear Ion Trap Mass Spectrometry
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76 Antioxidant and cytotoxic activity of Acanthus ilicifolius flower
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77 Anti-cancer potential of flavonoids: recent trends and future perspectives
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78 Apoptosis induction of human leukemia U937 cells by 7,8-dihydroxyflavone hydrate through modulation of the Bcl-2 family of proteins and the MAPKs signaling pathway
Hye Young Park,Gi-Young Kim,Taeg Kyu Kwon,Hye Jin Hwang,Nam Deuk Kim,Young Hyun Yoo,Yung Hyun Choi
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79 Grape juice concentrate protects reproductive parameters of male rats against cadmium-induced damage: a chronic assay
Vanessa Cardoso Pires,Andréa Pittelli Boiago Gollücke,Daniel Araki Ribeiro,Lisandro Lungato,Vânia DæAlmeida,Odair Aguiar
British Journal of Nutrition. 2013; : 1
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80 Potential Effects of Medicinal Plants and Secondary Metabolites on Acute Lung Injury
Daniely Cornélio Favarin,Jhony Robison de Oliveira,Carlo Jose Freire de Oliveira,Alexandre de Paula Rogerio
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81 Structure–cytotoxic activity relationship of 3-arylideneflavanone and chromanone (E,Z isomers) and 3-arylflavones
Bogumila Kupcewicz,Grazyna Balcerowska-Czerniak,Magdalena Malecka,Piotr Paneth,Urszula Krajewska,Marek Rozalski
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82 Cancer Chemoprevention by Polyphenols and Their Potential Application as Nanomedicine
SHAMS TABREZ,MEDHA PRIYADARSHINI,MARYAM UROOJ,SHAZI SHAKIL,GHULAM Md ASHRAF,MOHD SHAHNAWAZ KHAN,MOHAMMAD AMJAD KAMAL,QAMRE ALAM,NASIMUDEEN R. JABIR,ADEL MOHAMMAD ABUZENADAH,ADEEL G. A. CHAUDHARY,GHAZI ABDULLAH DAMANHOURI
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83 A Walnut-Enriched Diet Reduces the Growth of LNCaP Human Prostate Cancer Xenografts in Nude Mice
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84 Chemical and preclinical studies onHedyotis diffusawith anticancer potential
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85 Antimutagenicity Activity of Different Fractions of Zataria multiflora, Achillea wilhelmsii and Camellia sinensis using Ames Test
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86 Targeting DNA abasic site by myricetin: Sequence-dependent ESIPT emission
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87 Comparative Studies to Evaluate Relative in vitro Potency of Luteolin in Inducing Cell Cycle Arrest and Apoptosis in HaCaT and A375 Cells
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88 Delivering flavonoids into solid tumors using nanotechnologies
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89 Extracts of Crinum latifolium inhibit the cell viability of mouse lymph oma cell line EL4 and induce activation of anti-tumour activity of macrophages in vitro
Hoang-Yen T. Nguyen,Bach-Hue T. Vo,Lac-Thuy H. Nguyen,Jose Bernad,Mohamad Alaeddine,Agnes Coste,Karine Reybier,Bernard Pipy,Françoise Nepveu
Journal of Ethnopharmacology. 2013; 149(1): 75
[Pubmed] | [DOI]
90 Structure-cytotoxic activity relationship of 3-arylideneflavanone and chromanone (E,Z isomers) and 3-arylflavones
Kupcewicz, B. and Balcerowska-Czerniak, G. and Małecka, M. and Paneth, P. and Krajewska, U. and Rozalski, M.
Bioorganic and Medicinal Chemistry Letters. 2013; 23(14): 4102-4106
[Pubmed]
91 Antimutagenicity activity of different fractions of Zataria multiflora, Achillea wilhelmsii and Camellia sinensis using Ames test
Dehghan-Noodeh, G. and Sharififar, F. and Moshafi, M.H. and Behravan, E. and Dehghan-Noodeh, A. and Rezaei-Gharaeei, R.
Journal of Medical Sciences (Faisalabad). 2013; 13(6): 459-464
[Pubmed]
92 A walnut-enriched diet reduces the growth of LNCaP human prostate cancer xenografts in nude mice
Reiter, R.J. and Tan, D.-X. and Manchester, L.C. and Korkmaz, A. and Fuentes-Broto, L. and Hardman, W.E. and Rosales-Corral, S.A. and Qi, W.
Cancer Investigation. 2013; 31(6): 365-373
[Pubmed]
93 Comparative studies to evaluate relative in vitro potency of luteolin in inducing cell cycle arrest and apoptosis in HaCat and A375 cells
George, V.C. and Kumar, D.R.N. and Suresh, P.K. and Kumar, S. and Kumar, R.A.
Asian Pacific Journal of Cancer Prevention. 2013; 14(2): 631-637
[Pubmed]
94 Experimental and theoretical advances in functional understanding of flavonoids as anti-tumor agents
Babu, B.V. and Konduru, N.K. and Nakanishi, W. and Hayashi, S. and Ahmed, N. and Mitrasinovic, P.M.
Anti-Cancer Agents in Medicinal Chemistry. 2013; 13(2): 307-332
[Pubmed]
95 Apoptosis induction of human leukemia U937 cells by 7,8-dihydroxyflavone hydrate through modulation of the Bcl-2 family of proteins and the MAPKs signaling pathway
Park, H.Y. and Kim, G.-Y. and Kwon, T.K. and Hwang, H.J. and Kim, N.D. and Yoo, Y.H. and Choi, Y.H.
Mutation Research - Genetic Toxicology and Environmental Mutagenesis. 2013; 751(2): 101-108
[Pubmed]
96 Targeting DNA abasic site by myricetin: Sequence-dependent ESIPT emission
Xu, S. and Shao, Y. and Wu, F. and Liu, G. and Liu, L. and Peng, J. and Sun, Y.
Journal of Luminescence. 2013; 136: 291-295
[Pubmed]
97 Cancer chemoprevention by polyphenols and their potential application as nanomedicine
Tabrez, S. and Priyadarshini, M. and Urooj, M. and Shakil, S. and Ashraf, G.M. and Khan, M.S. and Kamal, M.A. and Alam, Q. and Jabir, N.R. and Abuzenadah, A.M. and Chaudhary, A.G.A. and Damanhouri, G.A.
Journal of Environmental Science and Health - Part C Environmental Carcinogenesis and Ecotoxicology Reviews. 2013; 31(1): 67-98
[Pubmed]
98 Antioxidant and cytotoxic activity of Acanthus ilicifolius flower
Firdaus, M. and Prihanto, A.A. and Nurdiani, R.
Asian Pacific Journal of Tropical Biomedicine. 2013; 3(1): 17-21
[Pubmed]
99 Structure Based Identification and Characterization of Flavonoids That Disrupt Human Papillomavirus-16 E6 Function
Jonathan J. Cherry,Anne Rietz,Anna Malinkevich,Yuqi Liu,Meng Xie,Matthew Bartolowits,V. Jo Davisson,James D. Baleja,Elliot J. Androphy,Zhi-Ming Zheng
PLoS ONE. 2013; 8(12): e84506
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100 In Vitro Action of Flavonoids in the Canine Malignant Histiocytic Cell Line DH82
Gabriel Silva,Ana Fachin,Renê Beleboni,Suzelei França,Mozart Marins
Molecules. 2013; 18(12): 15448
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101 Analysis and Antioxidant Capacity of Anthocyanin Pigments. Part II: Chemical Structure, Color, and Intake of Anthocyanins
Bueno, J.M., Sáez-Plaza, P., Ramos-Escudero, F., Jiménez, A.M., Fett, R., Asuero, A.G.
Critical Reviews in Analytical Chemistry. 2012; 42(2): 126-151
[Pubmed]
102 Analysis and Antioxidant Capacity of Anthocyanin Pigments. Part I: General Considerations Concerning Polyphenols and Flavonoids
# Bueno, J.M., Ramos-Escudero, F., Sáez-Plaza, P., Muñoz, A.M., Navas, M.J., Asuero, A.G.
Critical Reviews in Analytical Chemistry. 2012; 42(2): 102-125
[Pubmed]
103 Iron reduction potentiates hydroxyl radical formation only in flavonols
MacÁková, K. and Mladěnka, P. and Filipský, T. and Říha, M. and Jahodář, L. and Trejtnar, F. and Bovicelli, P. and Proietti Silvestri, I. and Hrdina, R. and Saso, L.
Food Chemistry. 2012; 135(4): 2584-2592
[Pubmed]
104 Diet, nutrients, phytochemicals, and cancer metastasis suppressor genes
Meadows, G.G.
Cancer and Metastasis Reviews. 2012; 31(3-4): 441-454
[Pubmed]
105 Characterization of flavonol inhibition of DnaB helicase: Real-time monitoring, structural modeling, and proposed mechanism
Lin, H.-H. and Huang, C.-Y.
Journal of Biomedicine and Biotechnology. 2012; 2012(735368)
[Pubmed]
106 Flavone potently stimulates an apical transporter for flavonoids in human intestinal Caco-2 cells
Lies, B. and Martens, S. and Schmidt, S. and Boll, M. and Wenzel, U.
Molecular Nutrition and Food Research. 2012; 56(11): 1627-1635
[Pubmed]
107 Tart cherry juice induces differential dose-dependent effects on apoptosis, but not cellular proliferation, in MCF-7 human breast cancer cells
Martin, K.R. and Wooden, A.
Journal of Medicinal Food. 2012; 15(11): 945-954
[Pubmed]
108 Autophagy Inhibitor Chloroquine Enhanced the Cell Death Inducing Effect of the Flavonoid Luteolin in Metastatic Squamous Cell Carcinoma Cells
Verschooten, L. and Barrette, K. and van Kelst, S. and Rubio Romero, N. and Proby, C. and de Vos, R. and Agostinis, P. and Garmyn, M.
PLoS ONE. 2012; 7(10)
[Pubmed]
109 Flavonoids as Chemopreventive and Therapeutic Agents Against Lung Cancer [Flavonoides como agentes quimiopreventivos y terapéuticos contra el cáncer de pulmón]
Cabrera, A. and Mach, N.
Revista Espanola de Nutricion Humana y Dietetica. 2012; 16(4): 143-153
[Pubmed]
110 Synthesis of substituted chalcones under solvent-free microwave irradiation conditions and their antimicrobial evaluation
Sharma, N. and Joshi, Y.C.
International Journal of Pharmacy and Pharmaceutical Sciences. 2012; 4(SUPPL. 4): 436-439
[Pubmed]
111 7,8-Dihydroxyflavone induces G1 arrest of the cell cycle in U937 human monocytic leukemia cells via induction of the Cdk inhibitor p27 and downregulation of pRB phosphorylation
Park, H.Y. and Kim, G.-Y. and Hyun, J.W. and Kim, N.D. and Kim, C.G. and Kim, W.-J. and Yoo, Y.H. and Choi, Y.H.
Oncology Reports. 2012; 28(1): 353-357
[Pubmed]
112 Protective effects of an extract from Citrus bergamia against inflammatory injury in interferon-gamma and histamine exposed human keratinocytes
Graziano, A.C.E. and Cardile, V. and Crascì, L. and Caggia, S. and Dugo, P. and Bonina, F. and Panico, A.
Life Sciences. 2012; 90(25-26): 968-974
[Pubmed]
113 7,8-Dihydroxyflavone exhibits anti-inflammatory properties by downregulating the NF-κB and MAPK signaling pathways in lipopolysaccharide-treated RAW264.7 cells
Park, H.Y. and Kim, G.-Y. and Hyun, J.W. and Hwang, H.J. and Kim, N.D. and Kim, B.-W. and Choi, Y.H.
International Journal of Molecular Medicine. 2012; 29(6): 1146-1152
[Pubmed]
114 Tart Cherry Juice Induces Differential Dose-Dependent Effects on Apoptosis, But Not Cellular Proliferation, in MCF-7 Human Breast Cancer Cells
Keith R. Martin,Alissa Wooden
Journal of Medicinal Food. 2012; 15(11): 945
[Pubmed] | [DOI]
115 Analysis and Antioxidant Capacity of Anthocyanin Pigments. Part II: Chemical Structure, Color, and Intake of Anthocyanins
Julia Martín Bueno,Purificación Sáez-Plaza,Fernando Ramos-Escudero,Ana Maria Jiménez,Roseane Fett,Agustin G. Asuero
Critical Reviews in Analytical Chemistry. 2012; 42(2): 126
[Pubmed] | [DOI]
116 Protective effects of an extract from Citrus bergamia against inflammatory injury in interferon-gamma and histamine exposed human keratinocytes
Adriana C.E. Graziano,Venera Cardile,Lucia Crascì,Sivia Caggia,Paola Dugo,Francesco Bonina,Annamaria Panico
Life Sciences. 2012; 90(25-26): 968
[Pubmed] | [DOI]
117 Characterization of Flavonol Inhibition of DnaB Helicase: Real-Time Monitoring, Structural Modeling, and Proposed Mechanism
Hsin-Hsien Lin,Cheng-Yang Huang
Journal of Biomedicine and Biotechnology. 2012; 2012: 1
[Pubmed] | [DOI]
118 Flavone potently stimulates an apical transporter for flavonoids in human intestinal Caco-2 cells
Barbara Lies,Stefan Martens,Sabine Schmidt,Michael Boll,Uwe Wenzel
Molecular Nutrition & Food Research. 2012; 56(11): 1627
[Pubmed] | [DOI]
119 Diet, nutrients, phytochemicals, and cancer metastasis suppressor genes
Gary G. Meadows
Cancer and Metastasis Reviews. 2012; 31(3-4): 441
[Pubmed] | [DOI]
120 Flavonoides como agentes quimiopreventivos y terapéuticos contra el cáncer de pulmón
Albert Cabrera,Núria Mach
Revista Española de Nutrición Humana y Dietética. 2012; 16(4): 143
[Pubmed] | [DOI]
121 Analysis and Antioxidant Capacity of Anthocyanin Pigments. Part I: General Considerations Concerning Polyphenols and Flavonoids
Julia Martín Bueno,Fernando Ramos-Escudero,Purificación Sáez-Plaza,Ana María Muñoz,María José Navas,Agustin G. Asuero
Critical Reviews in Analytical Chemistry. 2012; 42(2): 102
[Pubmed] | [DOI]
122 Iron reduction potentiates hydroxyl radical formation only in flavonols
Katerina Macáková,Premysl Mladenka,TomᚠFilipský,Michal Ríha,Ludek Jahodár,František Trejtnar,Paolo Bovicelli,Ilaria Proietti Silvestri,Radomír Hrdina,Luciano Saso
Food Chemistry. 2012; 135(4): 2584
[Pubmed] | [DOI]
123 Evaluation of Selected Flavonoids as Antiangiogenic, Anticancer, and Radical Scavenging Agents: An Experimental and In Silico Analysis
Rajesh N. Gacche,Harshala D. Shegokar,Dhananjay S. Gond,Zhenzhou Yang,Archana D. Jadhav
Cell Biochemistry and Biophysics. 2011; 61(3): 651
[Pubmed] | [DOI]
124 Evaluation of Selected Flavonoids as Antiangiogenic, Anticancer, and Radical Scavenging Agents: An Experimental and In Silico Analysis
# Gacche, R.N., Shegokar, H.D., Gond, D.S., Yang, Z., Jadhav, A.D.
Cell Biochemistry and Biophysics. 2011; 61(3): 651-663
[Pubmed]



 

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