Cf. Wang et Ms. Kurzer, EFFECTS OF PHYTOESTROGENS ON DNA-SYNTHESIS IN MCF-7 CELLS IN THE PRESENCE OF ESTRADIOL OR GROWTH-FACTORS, Nutrition and cancer, 31(2), 1998, pp. 90-100
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 eval
uated for their effects on DNA synthesis (estimated by thymidine incor
poration analysis) in estrogen-dependent MCF-7 cells in the presence o
f 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 syn
thesis, as did all compounds at >10 mu M, 2) tamoxifen enhanced genist
ein-induced DNA synthesis but inhibited DNA synthesis induced by all o
ther compounds, and 3) genistein enhanced insulin- and epidermal growt
h factor-induced DNA synthesis at 0.1-1.0 and 0.1-10 mu M, respectivel
y. At higher concentrations inhibition was observed. Similar effects w
ere 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 signific
antly enhanced E-2-induced and tyrosine kinase-mediated DNA synthesis;
at high concentrations, inhibition was observed. Differing effects we
re observed with the other compounds. The variable effects of phytoest
rogens an DNA synthesis must be considered when their roles in cancer
prevention or treatment are evaluated.