Prevention of mammary carcinogenesis in C3H/OuJ mice by green tea and tamoxifen

Background: Tamoxifen (TAM) is useful in the chemoprevention of breast cancer, and green tea catechins, including (-)-epigallocatechin gallate (EGCG), may have similar actions. In this study, we investigated their effects, alone or in combination, on mammary carcinogenesis using breast cancer cells and preneoplastic lesions inC3H/OuJ mice. Methods: Growth inhibitory effects of EGCG and TAM on MCF-7 cells were evaluated with the anchorage-independent colony forming assay. The effects on mammary tumor carcinogenesis and preneoplastic lesions were assessed in vivo using animals treated with GTE in drinking water (1%, 0.1%), or a tamoxifen pellet (10 mg/ animal, subcutaneously inoculated) or both agents in combination (1%GTE + 10 mg TAM). The number and size of mammary tumors were measured weekly during treatment. At 48 weeks of age, mice were sacrificed for the examination of hyperplastic alveolar nodules (HAN) and argyrophilic nucleolar organizer regions (AgNOR). Results: In the anchorage-independent growth assay, EGCG and TAM exhibited dose-dependent antiproliferative effects on MCF-7 cells. In the tumor formation assay, tumor incidences were decreased in the GTE, TAM, and GTE+TAM groups, particularly in the latter, in which no tumors developed. AgNOR counts were also significantly lower in the 1%GTE+TAM compared with the 1%GTE group, suggesting an additional anticarcinogenic effect. Conclusion: These data suggest that GTE and TAM, individually and in combination, have potential for chemoprevention of breast cancer.