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Phytoestrogen Concentration Determines Effects on DNA Synthesis in Human Breast Cancer Cells

Phytoestrogen Concentration Determines Effects on DNA Synthesis in Human Breast Cancer Cells

Chanfeng Wang and Mindy S. Kurzer,

Nutrition and Cancer 1997, 28(3), 236-247.

Abstract:

Thirteen isoflavonoids, flavonoids and lignans, including some known 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 most of the compounds at 20-80 µM sharply inhibited DNA synthesis in MDA-MD-231 cells. In MCF-7 cells, on the other hand, biphasic effects were seen. At 0.1-10 µM, coumestrol, genistein, biochanin A, apigenin, luteolin, kaempferol and enterolactone induced DNA synthesis 150-235% and at 20-90 µM, 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 concentration. 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 the compounds.

Inhibition of estrogen-dependent and independent breast cancer cells at high concentrations suggests additional mechanisms independent of the estrogen receptor.

The current focus on the role of phytoestrogens in cancer prevention must take into account the biphasic effects observed in this study, showing inhibition of DNA synthesis at high concentrations but induction at concentrations close to probable levels in humans.

Quotes from the paper

"Our data suggest the possibility that, at typical concentrations in humans, phytoestrogens and related flavonoids and lignans may stimulate, rather than inhibit, growth of estrogen-dependent tumours."

"In conclusion, most of the phytoestrogens and related compounds tested in this study showed stimulation of DNA synthesis in estrogen-dependent MCF-7 cells at low concentrations and inhibition of DNA synthesis in MCF-7 and estrogen-independent MDA-MB-231 cells at high concentrations. Although we observed inhibition at high levels, it is extremely important to consider that, at concentrations close to probable levels in humans, DNA synthesis was significantly induced in MCF-7 cells".