Proapoptotic potentials of genistein under growth stimulation by estrogen

In mammary carcinogenesis, hormonal effects have been reported to be important factors. Estrogens are known to regulate the proliferation of breast cancer cells, whereas genistein has been shown to induce apoptosis in mammary tumor cells. This study examined genistein-induced apoptosis through the regulation of bcl-2 and bax expression in the presence of estrogen. MCF-7 cells were treated with either genistein (25, 50, and 100 microM) or in the presence of 17beta-estradiol (12.5, 25, and 50 nM) for 48 h. DNA ladder analysis and Western blot analysis of bcl-2, bax, cyclin B(1), p21, and p53 were carried out. For comparison, the in vivo system was employed using estrogen-deficient and estrogen-sufficient female rats at two different concentrations of genistein. In MCF-7 cells, DNA fragmentation was evident by the treatment of genistein in the absence and presence of estrogen. Downregulation of bcl-2 and upregulation of bax by genistein were observed. However, genistein showed no proapoptotic properties in the presence of estrogen except with the lowest concentration of estrogen. In the presence of estrogen, p21 and p53 protein expression were upregulated by high concentrations of genistein. Bcl-2/bax ratios were decreased by genistein treatment in the presence or absence of estrogen in female rats. These results demonstrate that the proapoptotic property of genistein might be influenced greatly by the concentration of estrogen in vitro, but that this influence by estrogen is not evident in vivo.