Genistein inhibits growth of estrogen-independent human breast cancer cells in culture but not in athymic mice

The studies presented were conducted to assess the effect of the soy isofla vone genistein on proliferation of estrogen-independent human breast cancer cells (MDA-MB-231) in vitro and in vivo. Genistein (20 mu mol/L) inhibited cell proliferation in vitro by similar to 50%. Cell cycle progression was blocked in G(2)/M with 40 and 80 mu mol/L genistein. To evaluate the effect of dietary genistein on tumor growth in vivo, genistein was fed to female athymic mice inoculated with MDA-MB-231 cells. After solid tumor masses had formed, mice were fed genistein at a dose (750 mu g/g AIN-93G diet), shown to produce a total plasma genistein concentration of similar to 1 mu mol/L . This dose of genistein did not significantly (P > 0.05) alter tumor growt h. Studies were then conducted to assess the effect of dietary genistein on initial tumor development and growth. Genistein (750 mu g/g AIN-93G diet), fed 3 d before cells were inoculated into mice, did not significantly (P > 0.05) inhibit tumor formation or growth. The plasma concentration of genis tein in mice fed this dose of dietary genistein (750 mu g/g AIN-93G diet) d oes not appear sufficient to inhibit tumor formation or growth. Dietary gen istein at 750 mu g/g AIN-93G diet does not inhibit tumor formation or growt h. Additional studies were conducted to determine the effect of dietary dos ages ranging from 0 to 6000 mu g/g AIN-93G diet on plasma genistein concent ration. Plasma genistein concentration increased in a dose-dependent manner up to 7 mu mol/L at 6000 mu g/g AIN-93G diet. These data suggest that alth ough genistein inhibits cancer cell growth in vitro, it is unlikely that th e plasma concentration required to inhibit cancer cell growth in vivo can b e achieved from a dietary dosage of genistein.