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 (E2), tamoxifen, insulin, or epidermal growth factor. We observed that 1) at 0.01-10 μM, genistein and coumestrol enhanced E2-induced DNA synthesis, as did 10 μM enterolactone. Chrysin at 1.0-10 μM and 10 μM luteolin or apigenin inhibited E2-induced DNA synthesis, as did all compounds at >10 μM, 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 μM, respectively. At higher concentrations, inhibition was observed. Similar effects were seen with coumestrol. In conclusion, the effects of phytoestrogens in the presence of E2 or growth factors are concentration dependent and variable. At low concentrations, genistein and coumestrol significantly enhanced E2-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 on DNA synthesis must be considered when their roles in cancer prevention or treatment are evaluated.
Bibliographical noteFunding Information:
This work was performed in the Department of Food Science and Nutrition, University of Minnesota. It was supported in part by Minnesota Agricultural Experiment Station Project 18-34. These data were presented in part at the Experimental Biology Meeting in April 1997 and have been published in abstract form (FASEB J 11, A368, 1997). Address reprint requests to Dr. Mindy S. Kurzer, Dept. of Food Science and Nutrition, University of Minnesota, 1334 Eckles Ave., St. Paul, MN 55108. Phone: (612) 624-9789. FAX: (612) 625-5272. E-mail: firstname.lastname@example.org.