Flavonoids: Promising Anticancer Agents

Ren, Wenying; Qiao, Zhongdong; Wang, Hongwei; Zhu, Lei; Zhang, Li

doi:10.1002/chin.200338244

Cited by 88 publications

(112 citation statements)

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“…The contributors to flavonoid intake for the 66,940 women in our analysis were similar to the contributors for all participants in the Nurses' Health Study who completed the relevant FFQ. Although modifications Weighted by median of each quintile and calculated using the Wald test.-2 Total intake of five flavonoids (myricetin, kaempferol, quercetin, luteolin and apigenin).- 3 Median intake in milligrams/day; based on a single set of quintile cutpoints across all person-time.-4 Adjusted for age, duration of oral contraceptive use, parity, history of tubal ligation, smoking status, history of postmenopausal hormone use, physical activity, quintile of cumulative updated energy-adjusted lactose intake and cumulative updated total energy intake.- 5 Adjusted for above variables, plus quintile of intake of each other individual flavonoid.…”

Section: Resultsmentioning

confidence: 99%

“…Experimental evidence suggests that flavonoids have several potential anticarcinogenic characteristics, including antioxidant, antiestrogenic, antiproliferative and antiinflammatory properties. [2][3][4][5] Flavonoids are defined by their chemical structure, which includes 2 aromatic rings (the ''A'' and ''B'' rings) linked by a three-carbon bridge that comprises part of a third six-member ''C'' ring. 6 There are over 5,000 individual flavonoid compounds and at least 10 subclasses of flavonoids, which are characterized further by the structure of the C ring and the connection of the B and C rings.…”

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confidence: 99%

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A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer

Gates

Tworoger

Hecht

et al. 2007

Intl Journal of Cancer

265

168

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Flavonoids are antioxidant compounds found in plants, including fruits, vegetables and tea. No prior prospective studies have examined the association between intake of flavonoids in the flavonol and flavone subclasses and ovarian cancer risk. We analyzed the association between intake of 5 common dietary flavonoids and incidence of epithelial ovarian cancer among 66,940 women in the Nurses' Health Study. We calculated each participant's intake of myricetin, kaempferol, quercetin, luteolin and apigenin from dietary data collected at multiple time points, and used Cox proportional hazards regression to model the incidence rate ratio (RR) of ovarian cancer for each quintile of intake. Our analysis included 347 cases diagnosed between 1984 and 2002, and 950,347 personyears of follow-up. There was no clear association between total intake of the 5 flavonoids examined and incidence of ovarian cancer (RR 5 0.75 for the highest versus lowest quintile, 95% confidence interval [CI] 5 0.51-1.09). However, there was a significant 40% decrease in ovarian cancer incidence for the highest versus lowest quintile of kaempferol intake (RR 5 0.60, 95% CI 5 0.42-0.87; p-trend 5 0.002), and a significant 34% decrease in incidence for the highest versus lowest quintile of luteolin intake (RR 5 0.66, 95% CI 5 0.49-0.91; p-trend 5 0.01). There was evidence of an inverse association with consumption of tea (nonherbal) and broccoli, the primary contributors to kaempferol intake in our population. These data suggest that dietary intake of certain flavonoids may reduce ovarian cancer risk, although additional prospective studies are needed to further evaluate this association. If confirmed, these results would provide an important target for ovarian cancer prevention. ' 2007 Wiley-Liss, Inc.Key words: flavonoids; flavonols; flavones; diet; ovarian cancer There are few lifestyle factors known to reduce ovarian cancer risk, and no dietary exposure, with the possible exception of lactose, 1 has been clearly associated with risk. Flavonoids are polyphenol chemicals found naturally in fruits, vegetables, tea and other plant-derived foods and beverages. Experimental evidence suggests that flavonoids have several potential anticarcinogenic characteristics, including antioxidant, antiestrogenic, antiproliferative and antiinflammatory properties. [2][3][4][5] Flavonoids are defined by their chemical structure, which includes 2 aromatic rings (the ''A'' and ''B'' rings) linked by a three-carbon bridge that comprises part of a third six-member ''C'' ring. 6 There are over 5,000 individual flavonoid compounds and at least 10 subclasses of flavonoids, which are characterized further by the structure of the C ring and the connection of the B and C rings. 2,6,7 Flavonoids from 6 of these subclasses-flavones, flavonols, flavanols (catechins), flavanones, isoflavones and anthocyanidins-are common in the human diet. 2,7 Three studies have previously evaluated the association between dietary flavonoid intake and ovarian cancer risk. [8][9][10] However, only...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer

Gates

Tworoger

Hecht

et al. 2007

Intl Journal of Cancer

265

168

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“…These flavonoids are recognized to have anticancer and chemopreventive functions via antioxidant activity, inhibition of cell proliferation and angiogenesis, and induction of cellcycle arrest and apoptosis (13). Fisetin (3,7,3',4'-tetrahydroxyflavone), a naturally-occurring flavonoid, is widely distributed among edible vegetables and fruits such as apple, cucumber, grapes, kiwis, onion, persimmon and strawberry, the highest level of fisetin (160 μg/g wet food) being found in strawberries (14).…”

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confidence: 99%

Fisetin Induces Apoptosis of HSC3 Human Oral Cancer Cells Through Endoplasmic Reticulum Stress and Dysfunction of Mitochondria-mediated Signaling Pathways

Shih

Hung

Lee

et al. 2017

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Abstract. Background Western blotting was used to examine the levels of apoptotic-associated protein and results indicated that fisetin increased expression of pro-apoptotic proteins such as B-cell lymphoma 2 (BCL2) antagonist/killer (BAK) and BCL2-associated X (BAX) but reduced that of anti-apoptotic protein such as BCL2 and BCL-x, and increased the cleaved forms of caspase-3, -8 and -9, and cytochrome c, apoptosis-inducing factor (AIF) and endonuclease G (ENDO G) in HSC3 cells. Confocal microscopy showed that fisetin increased the release of cytochrome c, AIF and ENDO G from mitochondria into the cytoplasm. Conclusion: Based on these observations, we suggest that fisetin induces apoptotic cell death through endoplasmic reticulum stress-and mitochondria-dependent pathways.Oral cancer is a subtype of head and neck squamous cell carcinoma. Oral squamous cell carcinoma (OSCC) comprises of a large proportion of head and neck SCC (1). In men, oral cancer constitutes approximately 3% of all malignant 1103

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“…Beyond their antioxidant properties, many of these polyphenols are potent inhibitors of tyrosine kinases (5,(18)(19)(20)(21)(22)(23), act as either agonists or antagonists of estrogen receptors, or alter sex hormone production and metabolism (1,11,(24)(25)(26)(27). Furthermore, bioflavonoids display antiproliferative and proapoptotic effects, decrease the expression or function of several proteins that are involved in cell-cycle progression, and inhibit both the NF-kB and Akt signaling pathways (5,6,11,(28)(29)(30). Finally, a number of these compounds are potent topoisomerase II poisons (16,31,32).…”

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confidence: 99%

Bioflavonoids as Poisons of Human Topoisomerase IIα and IIβ

2007

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Bioflavonoids are human dietary components that have been linked to the prevention of cancer in adults and the generation of specific types of leukemia in infants. While these compounds have a broad range of cellular activities, many of their genotoxic effects have been attributed to their actions as topoisomerase II poisons. However, the activities of bioflavonoids against the individual isoforms of human topoisomerase II have not been analyzed. Therefore, we characterized the activity and mechanism of action of three major classes of bioflavonoids, flavones, flavonols, and isoflavones, against human topoisomerase IIR and II . Genistein was the most active bioflavonoid tested and stimulated enzymemediated DNA cleavage ∼10-fold. Generally, compounds were more active against topoisomerase II . DNA cleavage with both enzyme isoforms required a 5-OH and a 4′-OH and was enhanced by the presence of additional hydroxyl groups on the pendant ring. Competition DNA cleavage and topoisomerase II binding studies indicate that the 5-OH group plays an important role in mediating genistein binding, while the 4′-OH moiety contributes primarily to bioflavonoid function. Bioflavonoids do not require redox cycling for activity and function primarily by inhibiting enzyme-mediated DNA ligation. Mutagenesis studies suggest that the TOPRIM region of topoisomerase II plays a role in genistein binding. Finally, flavones, flavonols, and isoflavones with activity against purified topoisomerase IIR and II enhanced DNA cleavage by both isoforms in human CEM leukemia cells. These data support the hypothesis that bioflavonoids function as topoisomerase II poisons in humans and provide a framework for further analysis of these important dietary components.

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Flavonoids: Promising Anticancer Agents

Abstract: For Abstract see ChemInform Abstract in Full Text.

Cited by 88 publications

References 1 publication

A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer

A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer

Fisetin Induces Apoptosis of HSC3 Human Oral Cancer Cells Through Endoplasmic Reticulum Stress and Dysfunction of Mitochondria-mediated Signaling Pathways

Bioflavonoids as Poisons of Human Topoisomerase IIα and IIβ

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