The effect of genistein upon estrogen receptor negative human breast cancer cell growth in vitro and in vivo

The soybean derived isoflavone genistein has many biological activities including inhibition of cell growth. These studies present data on the in vitro and in vivo effects of genistein on the growth of estrogen independent MDA-MB-231 human breast cancer cells. Genistein (20 μM) inhibited cell proliferation in vitro by 50%. The cell cycle was blocked at G₂/M when 40 μM or 80 μM genistein was added to the medium. To evaluate the effect of genistein in vivo, female athymic mice were inoculated with MDA-MB-231 cells and fed (750 μg/g AIN-93G) genistein. Genistein at this dose did not affect tumor growth. When genistein was fed at 3000 μg/g to tumor bearing mice an inhibition of tumor growth was observed when compared to untreated control mice; however, there was approximately a 10% reduction in food intake in the genistein group. Although food intake was lower in the genistein treated mice compared to control mice there was no difference in weight gain. To assess the effect of dietary genistein on initial tumor development 750 μg genistein/g AIN-93G was fed before tumor cells were inoculated into the mice. This dose of genistein did not inhibit the development or growth of tumors. This research demonstrates that genistein inhibits in vitro MDA-MB-231 cell growth by blocking the cell cycle at G₂/M. Tumor growth in athymic mice fed genistein at 3000 μg/g AIN-93G was decreased. However it was not possible to determine whether the reduction in tumor growth was due to dietary genistein or the decrease in food intake.