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Effect of dietary flavonols on oestrogen receptor transactivation and cell death induction

Published online by Cambridge University Press:  09 March 2007

Lai K. Leung ,
Lai See Po ,
Tak Yee Lau  and
Yee Man Yuen
Lai K. Leung*
Affiliation:
Food and Nutritional Sciences Programme, The Chinese University of Hong Kong, Shatin N.T., Hong Kong Department of Biochemistry, The Chinese University of Hong Kong, Shatin N.T., Hong Kong
Lai See Po
Affiliation:
Department of Biochemistry, The Chinese University of Hong Kong, Shatin N.T., Hong Kong
Tak Yee Lau
Affiliation:
Department of Biochemistry, The Chinese University of Hong Kong, Shatin N.T., Hong Kong
Yee Man Yuen
Affiliation:
Department of Biochemistry, The Chinese University of Hong Kong, Shatin N.T., Hong Kong
*
*Corresponding author: Dr Lai K. Leung, fax +852 26037732, email laikleung@yahoo.com
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Abstract

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Consumption of fruits and vegetables has been associated with cancer prevention; flavonoids are widely distributed in plant foods and considered to be the active ingredients. Quercetin and kaempferol are two of the most commonly found dietary flavonols, and have been reported to prevent cancer. We have previously reported that the isoflavone genistein and the flavone baicalein exert differential actions on the oestrogen receptor (OR) α in HepG2 cells. Because of the structural resemblance to both isoflavone and flavone, we examined the effects of these dietary flavonols on ORα– and ORβ–specific transactivations and their subsequent involvement in inducing MCF-7 cell death. In the present study, both quercetin and kaempferol were able to compete for OR binding in a cell-free system and were agonistic to ORα and -β expressed in HepG2 cells, while some additive effect was observed in the oestrogen response element (ORE)-driven transcription when 17β-oestradiol was co-administered. Since the bcl-2 promoter contained two ORE, and ORE-driven transcriptional activity and Bcl-2 mRNA expression were increased by treatment with 10 μm-quercetin or kaempferol, it is possible that quercetin and kaempferol might up-regulate Bcl-2 expression through OR transactivation in MCF-7 cells. Cell death ELISA assay performed on MCF-7 cells indicated that an increase of apoptosis occurred at 25 μm-, but not 10 μm-, quercetin or kaempferol. Indirectly the results suggest that OR activation is not sufficient to induce apoptosis and that apoptosis is induced despite an increase in Bcl-2 expression.

Keywords

QuercertinKaempferolCell deathBcl-2Oestrogen receptor
Type
Research Article
Information
British Journal of Nutrition , Volume 91 , Issue 6 , June 2004 , pp. 831 - 839
Copyright
Copyright © The Nutrition Society 2004

References

Akagi, K, Hirose, M, Hoshiya, T, Mizoguchi, Y, Ito, N & Shirai, T (1995) Modulating effects of ellagic acid, vanillin and quercetin in a rat medium term multi-organ carcinogenesis model. Cancer Lett 94, 113–121.CrossRefGoogle Scholar
Breinholt, V & Larsen, JC (1998) Detection of weak estrogenic flavonoids using a recombinant yeast strain and a modified MCF-7 cell proliferation assay. Chem Res Toxicol 11, 622–629.CrossRefGoogle Scholar
Cermak, R, Landgraf, S & Wolffram, S (2003) The bioavailability of quercetin in pigs depends on the glycoside moiety and on dietary factors. J Nutr 133, 2802–2807.CrossRefGoogle ScholarPubMed
Chan, HY, Wang, H, Tsang, DSC, Chen, Z-Y & Leung, LK (2003) Screening of chemopreventive tea polyphenols against PAH genotoxicity in breast cancer cells by a XRE-Luciferase reporter construct. Nutr Cancer 46, 93–100.CrossRefGoogle ScholarPubMed
Choi, JA, Kim, JY, Lee, JY, Kang, CM, Kwon, HJ, Yoo, YD, Kim, TW, Lee, YS & Lee, SJ (2001) Induction of cell cycle arrest and apoptosis in human breast cancer cells by quercetin. Int J Oncol 19, 837–844.Google ScholarPubMed
Ciolino, HP, Daschner, PJ & Yeh, GC (1999) Dietary flavonols quercetin and kaempferol are ligands of the aryl hydrocarbon receptor that affect CYP1A1 transcription differentially. Biochem J 340, 715–722.CrossRefGoogle ScholarPubMed
Collins-Burow, BM, Burow, ME, Duong, BN & McLachlan, JA (2000) Estrogenic and antiestrogenic activities of flavonoid phytochemicals through estrogen receptor binding-dependent and -independent mechanisms. Nutr Cancer 38, 229–245.CrossRefGoogle ScholarPubMed
Cummings, SR, Eckert, S, Krueger, KA, Grady, D, Powles, TJ, Cauley, JA, Norton, L, Nickelsen, T, Bjarnason, NH, Morrow, M et al. (1999) The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. J Am Med Assoc 281, 2189–2197.CrossRefGoogle ScholarPubMed
Davis, SR, Dalais, FS, Simpson, ER & Murkies, AL (1999) Phytoestrogens in health and disease. Recent Prog Horm Res 54, 185–210.Google ScholarPubMed
de Vries, JH, Hollman, PC, Meyboom, S, Buysman, MN, Zock, PL, Van Staveren, WA & Katan, MB (1998) Plasma concentrations and urinary excretion of the antioxidant flavonols quercetin and kaempferol as biomarkers for dietary intake. Am J Clin Nutr 68, 60–65.CrossRefGoogle ScholarPubMed
Dechering, K, Boersma, C & Mosselman, S (2000) Estrogen receptors alpha and beta: two receptors of a kind? Curr Med Chem 7, 561–576.CrossRefGoogle ScholarPubMed
Delmas, PD, Bjarnason, NH, Mitlak, BH, Ravoux, AC, Shah, AS, Huster, WJ, Draper, M & Christiansen, C (1997) Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 337, 1641–1647.CrossRefGoogle Scholar
Gonzalez, FJ (2001) The use of gene knockout mice to unravel the mechanisms of toxicity and chemical carcinogenesis. Toxicol Lett 120, 199–208.CrossRefGoogle ScholarPubMed
Goodman, MT, Wilkens, LR, Hankin, JH, Lyu, LC, Wu, AH & Kolonel, LN (1997) Association of soy and fiber consumption with the risk of endometrial cancer. Am J Epidemiol 146, 294–306.CrossRefGoogle ScholarPubMed
Gross, A, McDonnell, JM & Korsmeyer, SJ (1999) Bcl-2 family members and the mitochondria in apoptosis. Genes Dev 13, 1899–1911.CrossRefGoogle ScholarPubMed
Han, D, Tachibana, H & Yamada, K (2001) Inhibition of environmental estrogen-induced proliferation of human breast carcinoma MCF-7 cells by flavonoids. In Vitro Cell Dev Biol Anim 37, 275–282.Google ScholarPubMed
Hollman, PC & Katan, MB (1999) Dietary flavonoids: intake, health effects and bioavailability. Food Chem Toxicol 37, 937–942.CrossRefGoogle ScholarPubMed
Ingram, D, Sanders, K, Kolybaba, M & Lopez, D (1997) Case-control study of phyto-oestrogens and breast cancer. Lancet 350, 990–994.CrossRefGoogle ScholarPubMed
Kuiper, GJM, Carlsson, B, Grandien, K, Enmark, E, Haggblad, J & Gustafsson, J-K (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors α and β. Endocrinology 138, 863–870.CrossRefGoogle ScholarPubMed
Le Bail, JC, Varnat, F, Nicolas, JC & Habrioux, G (1998) Estrogenic and anti-proliferative activities on MCF-7 human breast cancer cells by flavonoids. Cancer Lett 130, 209–216.CrossRefGoogle Scholar
Lee, MM, Lin, SS, Wrensch, MR, Adler, SR & Eisenberg, D (2000) Alternative therapies used by women with breast cancer in four ethnic populations. J Natl Cancer Inst 92, 42–47.CrossRefGoogle ScholarPubMed
Linford, NJ & Dorsa, DM (2002) 17beta-Estradiol and the phytoestrogen genistein attenuate neuronal apoptosis induced by the endoplasmic reticulum calcium-ATPase inhibitor thapsigargin. Steroids 67, 1029–1040.CrossRefGoogle ScholarPubMed
Lowe, SW & Lin, AW (2000) Apoptosis in cancer. Carcinogenesis 21, 485–495.CrossRefGoogle ScholarPubMed
Maggiolini, M, Bonofiglio, D, Marsico, S, Panno, ML, Cenni, B, Picard, D & Ando, S (2001) Estrogen receptor α mediates the proliferative but not the cytotoxic does-dependent effects of two major phytoestrogens on human breast cancer cells. Mol Pharmacol 60, 595–602.Google ScholarPubMed
Matsukawa, Y, Nishino, H, Okuyama, Y, Matsui, T, Matsumoto, T, Matsumura, S, Shimizu, Y, Sowa, Y & Sakai, T (1997) Effects of quercetin and/or restraint stress on formation of aberrant crypt foci induced by azoxymethane in rat colons. Oncology 54, 118–121.CrossRefGoogle ScholarPubMed
Miodini, P, Fioravanti, L, Di Fronzo, G & Cappelletti, V (1999) The two phyto-oestrogens genistein and quercetin exert different effects on oestrogen receptor function. Br J Cancer 80, 1150–1155.CrossRefGoogle ScholarPubMed
Morand, C, Manach, C, Crespy, V & Remesy, C (2000) Quercetin 3-O-beta-glucoside is better absorbed than other quercetin forms and is not present in rat plasma. Free Radic Res 33, 667–676.CrossRefGoogle Scholar
Mosmann, T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65, 55–63.CrossRefGoogle ScholarPubMed
Nenci, I, Marchetti, E & Querzoli, P (1988) Commentary on human mammary preneoplasia. The estrogen receptor-promotion hypothesis. J Steroid Biochem 30, 105–106.CrossRefGoogle ScholarPubMed
Perillo, B, Sasso, A, Abbondanza, C & Palumbo, G (2000) 17 β-estradiol inhibits apoptosis in MCF-7 cells, inducing bcl-2 expression via two estrogen-responsive elements present in the coding sequence. Mol Cell Biol 20, 2890–2901.CrossRefGoogle ScholarPubMed
Peterson, G & Barnes, S (1991) Genistein inhibition of the growth of human breast cancer cells: independence from estrogen receptors and the multi-drug resistance gene. Biochem Biophys Res Comm 179, 661–667.CrossRefGoogle ScholarPubMed
Po, LS, Chen, Z-Y, Tsang, DSC & Leung, LK (2002 a) Baicalein and genistein display differential actions on estrogen receptor (ER) transactivation and apoptosis in MCF-7 cells. Cancer Lett 187, 33–40.CrossRefGoogle ScholarPubMed
Po, LS, Wang, TTY, Chen, Z-Y & Leung, LK (2002 b) Genistein-induced apoptosis in MCF-7 cells involves changes in Bak and Bcl-x without evidence of anti-oestrogenic effects. Br J Nutr 88, 463–469.CrossRefGoogle Scholar
Reed, JC (1998) Bcl-2 family proteins. Oncogene 17, 3225–3236.CrossRefGoogle ScholarPubMed
Sesink, ALA, O'Leary, KA & Hollman, PCH (2001) Quercetin glucuronides but not glucosides are present in human plasma after consumption of quercetin-3-glucoside or quercetin-4'-glucoside. J Nutr 131, 1938–1941.CrossRefGoogle ScholarPubMed
So, FV, Guthrie, N, Chambers, AF & Carroll, KK (1997) 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 112, 127–133.CrossRefGoogle ScholarPubMed
Soleas, GJ, Goldberg, DM, Gras, L, Levesque, M & Diamandis, EP (2001) Do wine polyphenols modulate p53 gene expression in human cancer cell lines? Clin Biochem 34, 415–420.CrossRefGoogle ScholarPubMed
Tham, DM, Gardner, CD & Haskell, WL (1998) Clinical review 97: Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab 83, 222–335.Google ScholarPubMed
Wang, TTY & Phang, JM (1995) Effects of estrogen on apoptotic pathways in human breast cancer cell line MCF-7. Cancer Res 55, 3902–3907.Google ScholarPubMed