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Phytoestrogen
Concentration Determines Effects on DNA Synthesis in Human Breast
Cancer Cells Chanfeng Wang and Mindy S. Kurzer, Nutrition and Cancer, 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
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