Interactions between phytoestrogens and estradiol show variable effects on growth of estrogen-dependent MCF-7 cells

Isoflavones and lignans are diphenolic compounds commonly consumed in vegetables and fruits. A number of these compounds have been shown to exert estrogen-like effects and thus are considered phytoestrogens. Phytoestrogens have been proposed to exert antiestrogenic effects in the presence of estradiol (E₂); these antiestrogenic effects have been suggested to contribute to dietary prevention of estrogen-dependent carcinogenesis. In this study, the interactions of 6 phytoestrogens and related compounds with estradiol (E₂) were evaluated by incubating estrogen-dependent MCF-7 cells with E₂ and each phytoestrogen. 0.01-10 μM genistein significantly increased 0.001-1.0 μM E₂-induced cell growth by 20-190%; 0.01-10 μM coumestrol significantly increased 0.01-10 nM E₂-induced cell growth by 20-60%; and 0.5-10 μM enterolactone significantly increased 0.01 nM E₂-induced growth by 16-27%. Addition of 10 μM luteolin significantly inhibited 0.1-1.0 μM E₂-induced growth by 10-20%; 1.0-10 μM chrysin and apigenin significantly inhibited E₂-stimulated growth by 30-60% and 10-35%. respectively. While E₂-induced cell growth was not affected by 6-day pretreatment with genistein or coumestrol, the additive effects of genistein and coumestrol on E₂-induced growth were inhibited by pretreatment with E₂ for 6 days. In conclusion, the interactions of phytoestrogens with E₂ are variable. Although some related compounds blocked E₂-induced cell growth, genistein, coumestrol and enterolactone stimulated cell growth in the presence of E₂. The variable effects of interactions between phytoestrogens and E₂ on growth of estrogen-dependent cells must be considered when evaluating their roles in cancer prevention.