Green tea extracts decrease carcinogen-induced mammary tumor burden in rats and rate of breast cancer cell proliferation in culture

Epidemiological evidence suggests tea (Camellia sinensis L.) has chemopreve ntive effects against various tumors. Green tea contains many polyphenols, including epigallocatechin-3 gallate (EGCG), which possess antioxidant qual ities. Reduction of chemically induced mammary gland carcinogenesis by gree n tea in a carcinogen-induced rat model has been suggested previously, but the results reported were not statistically significant. Here we have teste d the effects of green tea on mammary tumorigenesis using the 7,12-dimethyl benz(a)anthracene (DMBA) Sprague-Dawley (S-D) rat model. We report that gre en tea significantly increased mean latency to first tumor, and reduced tum or burden and number of invasive tumors per tumor-bearing animal; although, it did not affect tumor number in the female rats. Furthermore, we show th at proliferation and/or viability of cultured Hs578T and MDA-MB-231 estroge n receptor-negative breast cancer cell lines was reduced by EGCG treatment. Similar negative effects on proliferation were observed with the DMBA-tran sformed D3-1 cell line. Growth inhibition of Hs578T cells correlated with i nduction of p27(Kip1) cyclin-dependent kinase inhibitor (CKl) expression. H s578T cells expressing elevated levels of p27(Kip1) protein due to stable e ctopic expression displayed increased G1 arrest. Thus, green tea had signif icant chemopreventive effects on carcinogen-induced mammary tumorigenesis i n female S-D rats. In culture, inhibition of human breast cancer cell proli feration by EGCG was mediated in part via induction of the p27(Kip1) CKl. ( C) 2001 Wiley-Liss.