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Effect of Genistein on In Vitro and In Vivo Models of Cancer^1,2,

Departments of Pharmacology and Biochemistry, University of Alabama at Birmingham, Birmingham, AL 35294

In two–thirds of studies of the effect of genistein-containing soy materials in animal models of cancer, the risk of cancer (incidence, latency or tumor number) was significantly reduced. In addition, purified genistein delayed mammary tumor appearance in association with increased cell differentiation in mammary tissue in rats treated with 7,12-dimethylbenz[a]anthracene when administered neonatally, inhibited phorbol ester-induced H₂O₂ production in a model of skin cancer, and inhibited aberrant crypt formation in a model of colonic cancer. In in vitro models, genistein inhibited the proliferation of human tumor cell lines in culture with a wide variation in IC₅₀ values (2.6–79 µmol/L, or 1–30 µg/mL). In only a few cases was the IC₅₀ below 13.2 µmol/L (5 µg/mL), the presumed upper limit for the serum genistein concentration in those on a high-soy diet. In future studies, greater emphasis should be placed on the effect of genistein on nontransformed, normal cell lines from the tissues where cancer can occur rather than established tumor cell lines. Similarly, the effect of genistein on the progression and/or promotion of cancer may be more clearly examined using nontransformed cell lines transfected with specific oncogenes thought to be activated during oncogenesis.

KEY WORDS: • isoflavones • chemoprevention • cell cultures • animal models

¹ Presented at the First International Symposium on the Role of Soy in Preventing and Treating Chronic Disease, held in Mesa, AZ, February 20–23, 1994. The symposium was sponsored by Protein Technologies International, the soybean growers from Nebraska, Indiana and Iowa and the United Soybean Board. Guest editors for this symposium were Mark Messina, 1543 Lincoln Street, Port Townsend, WA 98368, and John W. Erdman, Jr., Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801-3852.

² Research on soy and a reduction in cancer risk has been supported by grants from the American Cancer Society (BC-599), the American Institute for Cancer Research (91B58, MG92A42), the United Soybean Board, the Nebraska Soybean Board, the National Cancer Institute (1R01 CA61668) and Protein Technologies International of St. Louis, MO.

³ To whom all correspondence should be addressed.