Phytoestrogen Concentration Determines Effects on DNA Synthesis in Human Breast Cancer Cells.
Phytoestrogen Concentration Determines Effects on DNA Synthesis in Human Breast Cancer Cells.
Year: 1997
Authors: C Wang, M S Kurzer.
Publication Name: Nutr. Cancer.
Publication Details: Volume 28; Number 3; 236.
Abstract:
In vitro experiments have shown that specific phytoestrogens inhibit tumor cell growth. Animal studies have indicated that phytoestrogens are protective against experimentally induced cancer of the mammary gland and the colon. Phytoestrogens may contribute to a reduction in breast cancer in part due to anti-estrogenic effects that include competition with estradiol for binding to estrogen receptors and inhibition of estrogen synthesis. Phytoestrogens may also have nonhormonal properties that result in anti-cancer activity. The objective of the present study was to examine the effects of low and high concentrations of various phytoestrogens on DNA synthesis (generally believed to reflect cell proliferation) in breast cancer cells. The compounds studied included the isoflavonoids genistein, biochanin A, daidzein, and coumestrol; the flavonoids flavone, luteolin, apigenin and chrysin; the flavonols kaempferol and quercetin; rutin and catechin and the enterolactone. The phytoestrogens were evaluated for their effects on DNA synthesis in estrogen-dependent (MCF-7) and -independent (MDA-MB-231) human breast cancer cells. Treatment for 24 hours with the majority of phytoestrogens at a concentration of 20-80 microM sharply inhibited DNA synthesis in estrogen- independent (MDA-MB-231) human breast cancer cells. In estrogen-dependent (MCF-7) human breast cancer cells, on the other hand, biphasic effects were seen. At 0, 1-10 mM, coumestrol, genistein, biochanin A, apigenin, luteolin, kaempferol, and enterolactone induced DNA synthesis 150-235% and, at 20-90 mM, inhibited DNA synthesis by 50%. Treatment of MCF-7 cells for 10 days with genistein or coumestrol showed continuous stimulation of DNA synthesis at low concentrations. Time-course experiments with genistein in MCF-7 cells showed effects to be reversed by 48-hour withdrawal of genistein at most concentrations. Induction of DNA synthesis in MCF-7 cells, but not in MDA-MB-231 cells, is consistent with an estrogenic effect of these compounds. The authors concluded that the inhibition of estrogen-dependent and independent breast cancer cells at high concentrations by various phytoestrogens indicates that additional mechanisms independent of effects on the estrogen receptor may be involved in the anti-carcinogenic activities of these compounds. The results showed that some phytoestrogens inhibit DNA synthesis at high concentrations but cause induction of DNA synthesis at concentrations close to probable levels in the current human diet. The investigators recommend that the current focus on the role of phytoestrogens in cancer prevention must take into account the biphasic effects of some of these compounds as observed in this study. However, the authors also recognize that the situation in vivo is more complex than the protocol used in this experiment and that the effects observed in this study represent only a few of the multiple mechanisms by which phytoestrogens may influence tumor growth. Further studies are recommended to clarify the effects of phytoestrogens at typical dietary levels in the presence and absence of estrogens as well as possible synergistic effects.
