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-dependent human breast cancer (MCF-7) cells in vivo. Genistin is the glycoside form of genistein and the predominant form found in plants. It is generally believed that genistin is metabolized to the aglycone genistein in the lower gut. However, it is unclear if the rate of metabolism of genistin to genistein is sufficient to produce a level of genistein capable of stimulating estrogen-dependent breast cancer cell growth. Our hypothesis was that dietary genistin would stimulate tumor growth similar to that observed with genistein in athymic mice. To test this hypothesis, genistin or genistein was fed to athymic mice containing xenografted estrogen-dependent breast tumors (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 weeks. At completion of the study, half of the animals per treatment group were killed and tumors collected for evaluation of cellular proliferation and estrogen-responsive pS2 gene expression. Incorporation of bromo-deoxyuridine into cellular DNA was utilized as an indicator of cellular proliferation. Dietary genistin resulted in increased tumor growth, pS2 expression and cellular proliferation similar to that observed with genistein. The remaining mice were switched to diets free of genistin and genistein. When mice were placed on isoflavone free diets, tumors regressed over a span of 9 weeks. Next, we examined how effectively and where metabolism of genistin to genistein occurred in the digestive tract. We present evidence that demonstrates conversion of genistin to its aglycone form genistein begins in the mouth and then continues in the small intestine. Both human saliva and the intestinal cell-free extract from mice converted genistin to genistein. In summary, the glycoside genistin, like the aglycone genistein, can stimulate estrogen-dependent breast cancer cell growth in vivo. Removal of genistin or genistein from the diet caused tumors to regress.
Allred
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CD
Department of Food Science and Human Nutrition and Division of Nutritional Sciences, University of Illinois, at Urbana-Champaign, IL 61801, USA.
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Allred
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Chang
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Helferich
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WG
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage*; D005260:Female; D019833:Genistein / Q000008:administration & dosage*; D006801:Humans; D015151:Immunoblotting; D007421:Intestine, Small / Q000187:drug effects; D007529:Isoflavones / Q000008:administration & dosage*; D051379:Mice; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000071163:Trefoil Factor-1; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D000970:Antineoplastic Agents; D004967:Estrogens; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D011506:Proteins; D012333:RNA, Messenger; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; C040641:genistin; D019833:Genistein