Dietary genistin stimulates growth of estrogen-dependent breast cancer tumors similar to that observed with genistein

The estrogenic soy isoflavone, genistein, stimulates growth of estrogen-dep endent human breast cancer (MCF-7) cells in vivo. Genistin is the glycoside form of genistein and the predominant form found in plants. It is generall y believed that genistin is metabolized to the aglycone genistein in the lo wer gut. However, it is unclear if the rate of metabolism of genistin to ge nistein is sufficient to produce a level of genistein capable of stimulatin g estrogen-dependent breast cancer cell growth. Our hypothesis was that die tary genistin would stimulate tumor growth similar to that observed with ge nistein in athymic mice. To test this hypothesis, genistin or genistein was fed to athymic mice containing xenografted estrogen-dependent breast tumor s (MCF-7). Mice were fed either genistein at 750 p.p.m. (parts per milllion ) or genistin at 1200 p.p.m., which provides equal molar concentrations of aglycone equivalents in both diets. Tumor size was measured weekly for 11 w eeks. At completion of the study, half of the animals per treatment group w ere killed and tumors collected for evaluation of cellular proliferation an d estrogen-responsive pS2 gene expression. Incorporation of bromo-deoxyurid ine into cellular DNA was utilized as an indicator of cellular proliferatio n. Dietary genistin resulted in increased tumor growth, pS2 expression and cellular proliferation similar to that observed with genistein. The remaini ng mice were switched to diets free of genistin and genistein. When mice we re placed on isoflavone free diets, tumors regressed over a span of 9 weeks . Next, we examined how effectively and where metabolism of genistin to gen istein occurred in the digestive tract. We present evidence that demonstrat es conversion of genistin to its aglycone form genistein begins in the mout h and then continues in the small intestine. Both human saliva and the inte stinal cell-free extract from mice converted genistin to genistein. In summ ary, the glycoside genistin, like the aglycone genistein, can stimulate est rogen-dependent breast cancer cell growth in vivo. Removal of genistin or g enistein from the diet caused tumors to regress.