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Inhibition of environmental estrogen-induced proliferation of human breast carcinoma MCF-7 cells by flavonoids

  • Toxicology/Chemical Carcinogenesis
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Summary

In the present study, we evaluated the individual and combined effects of environmental estrogens and flavonoids on the proliferation of human breast carcinoma MCF-7 cells. These compounds are as follows: (1) pharmaceutical chemicals such as diethylstilbestrol, 17α-ethynylestradiol (17ES), tamoxifen, mestranol, and clomiphene, (2) industrial chemicals such as bisphenol A (BisA), 4-octylphenol (OP), 4-nonylphenol (NP), andp,p′-biphenol, and (3) flavonoids such as daidzein (D), genistein (G), quercetin (Q), and luteolin (L). We found that nanomolar concentrations of 17ES, BisA, OP, and NP were sufficient to stimulate the proliferation of MCF-7 cells. Among then, 1 μM BisA exhibited cell proliferation-stimulating activity as strong as 10 nM 17β-estradiol; and D and G exhibited cell proliferation-stimulating activity at 10 nM. On the other hand, Q and L exhibited cell proliferation-inhibiting activity. We also found that 10 nM flavonoids, such as D, G, Q, and L, were able to inhibit the proliferation-stimulating activity in MCF-7 cells by 1 μM environmental estrogens.

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References

  • Adlercruetz, H. Western diet and western disease: some hormonal and biochemical mechanisms and associations. Scand. J. Clin. Lab. Invest. 50:3–10; 1990.

    Google Scholar 

  • Barkly, B. W.; William, H. K.; Nicoleno, G. Effects of serum and insulin on the sensitivity of the human breast cancer cell line MCF-7 to estrogens and antiestrogens. Cancer Res. 41:82–88; 1981.

    Google Scholar 

  • Bradbury, R. B.; White, D. E. Oestrogens and related substances in plants. Vitam. Horm. 12:207–233; 1954.

    Article  PubMed  CAS  Google Scholar 

  • Cheng, E.; Yoder, L.; Story, C. D.; Burrough, W. Estrogenic activity of some isoflavone derivatives. Science 120:545–546; 1954.

    Article  Google Scholar 

  • Clark, J. H.; Maraverch, B. M. The agonistic-antagonistic properties of clomiphene: a review. Pharmacol. Ther. 17:467–489; 1982.

    Article  Google Scholar 

  • Colborn, T.; Dumanoski, D.; Myers, J. P. Our stolen future. New York: Penguin Books; 1996:76.

    Google Scholar 

  • Colborn, T.; Von Seal, F. S.; Soto, A. M. Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ. Health Perspect. 101:378–384; 1993.

    Article  PubMed  CAS  Google Scholar 

  • Cook, N. C.; Samman, S. Flavonoids-chemistry, metabolism, cardioprotective effects, and dietary sources. J. Nutr. Biochem. 7:66–76; 1996.

    Article  CAS  Google Scholar 

  • Farnsworth, N. R.; Bingel, A. S.; Cordell, G. A.; Crane, F. A.; Fong, H. H. S.: Potential value of plants as sources of new antifertility agents II. J. Pharm. Sci. 64:717–754; 1975.

    Article  PubMed  CAS  Google Scholar 

  • Fisher, S.; Cameron, G. S.; Baldwin, J. K.; Jasheway, D. W.; Patrick, K. E. Reactive oxygen in the tumor promotion stage of skin carcinogenesis. Lipids 23:592–597; 1988.

    Article  Google Scholar 

  • Fotsis, T.; Pepper, M. S.; Aktas, E., et al Flavonoids, dietary-derived inhibitors of cell proliferation and in vitro angiogenesis. Cancer Res. 57:2916–2921; 1997.

    PubMed  CAS  Google Scholar 

  • Guillette, L. Endocrine disrupting environmental contaminants and developmental abnormalities in embryos. Hum. Ecol. Risk Assess. 1:25–36; 1995.

    CAS  Google Scholar 

  • Ingram, D.; Sandres, K.; Kolybata, M.; Lopez, D. Case-control study of phytoestrogens and breast cancer. Lancet 350:990–994; 1997.

    Article  PubMed  CAS  Google Scholar 

  • Katsuze, N.; Hogo, A.; Armelin, H. A.; Gorden, S. Control of ovarian cell growth in culture by serum and pituitary factors. Proc. Natl. Acad. Sci. 72(2):483–487; 1975.

    Article  Google Scholar 

  • Katzenellenbogan, B. S.; Bhakoo, H. S.; Ferguson, E. R.; Lan, N. C.; Tatee, T.; Tsai, T. S.; Katzenellenbogan, J. A. Estrogen and anti-estrogen action in reproductive tissues and tumors. Recent Prog. Horm. Res. 35:258–265; 1979.

    Google Scholar 

  • Kurzer, M. S.; Xu, X. Dietary phytoestrogens. Annu. Rev. Nutr. 17:353–381; 1997.

    Article  PubMed  CAS  Google Scholar 

  • Leclerg, G.; Heuson, J. C. Physiological and pharmacological effects of estrogens in breast cancer. Biochim. Biophys. Acta 560:427–455; 1979.

    Google Scholar 

  • Lee, H. P.; Gourley, L.; Duffy, S. W.; Esteve, J.; Lee, J.; Day, N. E. Dietary effects on breast cancer risk in Singapore. Lancet 337:1197–1200; 1991.

    Article  PubMed  CAS  Google Scholar 

  • Levenson, A. S.; Jordan, V. C. MCF-7: the first hormone responsive breast cancer cell line. Cancer Res. 57:3071–3078; 1997.

    PubMed  CAS  Google Scholar 

  • Luman, C. B.; Klopper, A. Antiestrogens: a review. Clin. Endocrinol. (Oxf.) 4:551–558; 1975.

    Google Scholar 

  • Makela, S.; Davis, V. L.; Tally, W. C.; Korkman, J.; Salo, L.; Vihko, R.; Santti, R.; Korach, K. S. Dietary estrogens act through estrogen receptor-mediated processes and show no antiestrogenicity in cultured breast cancer cells. Environ. Health Perspect. 102:572–581; 1994.

    PubMed  CAS  Google Scholar 

  • Makela, S. I.; Pylkkanen, L. H.; Santti, R. S. S.; Adlercreutz, H. Dietary soybean may be antiestrogenic in male mice. J. Nutr. 125:437–445; 1995.

    PubMed  CAS  Google Scholar 

  • Markiewicz, L.; Garey, J.; Adlercreutz, H.; Gurpide, E.In vitro bioassays of non-steroidal phytoestrogens. J. Steroid Biochem. Mol. Biol. 45:339–405; 1993.

    Article  Google Scholar 

  • Messina, M.; Barnes, S.; Setchell, K. D. R. Phytoestrogens and breast cancer—commentary. Lancet 350:971–972; 1997.

    Article  PubMed  CAS  Google Scholar 

  • Messina, M. J.; Persky, V.; Setchell, K. D. R.; Barnes, S. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr. Cancer 21:113–131; 1994.

    PubMed  CAS  Google Scholar 

  • Miksicek, R. J. Commonly occurring plant flavonoids have estrogenic activity. Mol. Pharmacol. 44:37–43; 1993.

    PubMed  CAS  Google Scholar 

  • Mitchell, J. H.; Gardner, P. T.; McPhail, D. B.; Morrice, P. C.; Collins, A. R.; Duthie, G. G. Antioxidant efficacy of phytoestrogens in chemical and biological model systems. Arch. Biochem. Biophys. 360(1):142–148; 1998.

    Article  PubMed  CAS  Google Scholar 

  • Murphy, P. A. Phytoestrogen content of processed soybean products. Food Technol. 36:62–64; 1982.

    Google Scholar 

  • Price, K. R.; Fenwick, G. R. Naturally ocurring oestrogens in food. A review. Food Addit. Contam. 2:73–106; 1985.

    PubMed  CAS  Google Scholar 

  • Richard, L. E.; Benita, S. K. Effects of estrogens and antiestrogens on estrogen receptors dynamics and cancer cells. Cancer Res. 42:139–144; 1981.

    Google Scholar 

  • Ruh, M. F.; Zacharewski, T.; Connor, K.; Howell, J.; Chen, I.; Safe, S. Naringenin, a weakly estrogenic bioflavonoid that exihibits antiestrogenic activity. Biochem. Pharmacol. 50:1485–1493; 1995.

    Article  PubMed  CAS  Google Scholar 

  • Safe, S. Do environmental estrogens play a role in development of breast cancer in wome and male reproductive problems? Hum. Ecol. Risk Assess. 1(2):17–23; 1995.

    CAS  Google Scholar 

  • Setchell, K. D. R. Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. Am. J. Clin. Nutr. 68(S): 1333–1346; 1998.

    Google Scholar 

  • Setchell, K. D. R.; Adlercreutz, H. Mammalian ligands and phytoestrogens. Recent studies on their formation, metabolism and biological role in health and disease. In: Rowlanol, I. R., ed. Role of the gut flora in toxicity and cancer. London: Academic Press; 1988.

    Google Scholar 

  • Setchell, K. D. R.; Borriello, S. P.; Hulme, P.; Kirk, D. N.; Axelson, M. Nonsteroidal estrogens of dietary origin: possible roles in hormone-dependent disease. Am. J. Clin. Nutr. 40:569–578; 1984.

    PubMed  CAS  Google Scholar 

  • Setchell, K. D. R.; Fenwick, G. R. Naturally occurring non-steroidal estrogens of dietary origin. In: Mclachlan, J., ed. Estrogens in the environment: influence on development. New York: Elsevier; 1985;69–85.

    Google Scholar 

  • Sharpe, R.; Skakkenback, N. E. Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet 341: 1392–1395; 1993.

    Article  PubMed  CAS  Google Scholar 

  • Soto, A. M.; Justicia, H.; Wray, J. W.; Sonnenchein, C.p-Nonyl-phenol: an estrogenic xenobiotic released from “modified” polytyrene. Environ. Health Perspect. 92:167–173; 1991.

    Article  PubMed  CAS  Google Scholar 

  • Soto, A. M.; Sonnenschein, C.; Chung, K. L.; Fernadez, M. F.; Olea, N.; Serrano, F. O. The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants [Estrogens in the environment. Proceedings of the Estrogens in the Environmental III: Global Health Implications Conference]. Environ. Health Perspect. 103(S):113–122; 1995.

    Article  PubMed  CAS  Google Scholar 

  • Stob, M. Naturally occurring food toxicants: oestrogens. In: Dechrigol Jr., M., ed. Handbook of naturally occurring food toxicants. Boca Raton, FL: CRC Press; 1983:81–100.

    Google Scholar 

  • Sutherland, R. L. Estrogen antagonists in chick oviduct: antagonist activity of eight synthetic triphenlyethylene derivatives and their interactions with cytoplasmic and nuclear estrogen receptors. Endocrinol. 109:2061–2067; 1981.

    Article  CAS  Google Scholar 

  • Sutherland, R. L.; Mester, J.; Banliew, E. E. Tamoxifen is a potent “pure” antiestrogen in the chick oviduct. Nature 267:434–436; 1977.

    Article  PubMed  CAS  Google Scholar 

  • Terenius, L. Structure activity relationships of antiestrogens with regard to interaction with 17β-estradiol in the mouse uterus and vagina. Acta Endocrinol. 66:402–431; 1971.

    Google Scholar 

  • Wang, W.; Carl, M.; Higuchi, Rongging, Z. Individual and combinatory effects of soy isoflavones on thein vitro protenuation of lymphocyte activation. Nutr. Cancer 29(1):29–34; 1997.

    Article  PubMed  CAS  Google Scholar 

  • Wang, X. U.; Murphy, P. A.; Cook, L.; Hendrich, S. Daidzein is a more bioavailable soymilk isoflavone than is genistein in adult women. J. Nutr. 124:825–832; 1994.

    PubMed  Google Scholar 

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Correspondence to Koji Yamada.

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Han, DH., Tachibana, H. & Yamada, K. Inhibition of environmental estrogen-induced proliferation of human breast carcinoma MCF-7 cells by flavonoids. In Vitro Cell.Dev.Biol.-Animal 37, 275–282 (2001). https://doi.org/10.1007/BF02577543

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