Effects of phytoestrogens on DNA synthesis in MCF-7 cells in the presence of estradiol or growth factors

Phytoestrogen effects on estrogen action and tyrosine kinase activity have been proposed to contribute to cancer prevention. To study these mechanisms, a number of phytoestrogens and related compounds were evaluated for their effects on DNA synthesis (estimated by thymidine incorporation analysis) in estrogen-dependent MCF-7 cells in the presence of estradiol (E-2), tamoxifen, insulin, or epidermal growth factor. We observed that 1) at 0.01-10 mu M, genistein and coumestrol enhanced E-2-induced DNA synthesis, as did 10 mu M enterolactone. Chrysin at 1.1-10 mu M and 10 mu M luteolin or apigenin inhibited E-2-induced DNA synthesis, as did all compounds at >10 mu M, 2) tamoxifen enhanced genistein-induced DNA synthesis but inhibited DNA synthesis induced by all other compounds, and 3) genistein enhanced insulin- and epidermal growth factor-induced DNA synthesis at 0.1-1.0 and 0.1-10 mu M, respectively. At higher concentrations inhibition was observed. Similar effects were seen with coumestrol. In conclusion, the effects of phytoestrogens in the presence of E-2 Or growth factors are concentration dependent and variable. At low concentrations, genistein and coumestrol significantly enhanced E-2-induced and tyrosine kinase-mediated DNA synthesis; at high concentrations, inhibition was observed. Differing effects were observed with the other compounds. The variable effects of phytoestrogens an DNA synthesis must be considered when their roles in cancer prevention or treatment are evaluated.