Carcinogenesis Advance Access originally published online on June 19, 2006
Carcinogenesis 2006 27(12):2424-2433; doi:10.1093/carcin/bgl066
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The combination of green tea and tamoxifen is effective against breast cancer
1 Department of Surgery, University of California, Los Angeles CA 90095, USA
2 Department of Medicine, Division of Oncology, University of California, Los Angeles CA 90095, USA
3 Center for Human Nutrition, University of California, Los Angeles CA 90095, USA
4 Department of Pathology, University of California, Los Angeles CA 90095, USA
*To whom correspondence should be addressed at: Department of Surgery, Division of Oncology, University of California, Box 951782, Los Angeles, CA 90095-1782, USA. Tel: +1 310 206 2215; Fax: +1 310 825 7575; Email: maibrooks{at}mednet.ucla.edu
Epidemiologic data have suggested that green tea may prevent breast cancer. Studies in our laboratory have provided evidence that green tea extract inhibits breast cancer growth by a direct anti-proliferative effect on the tumor cells, as well as by indirect suppressive effects on the tumor-associated endothelial cells. In this study, we asked whether concurrent administration of green tea may add to the anti-tumor effects of standard breast cancer therapy. We observed that green tea increased the inhibitory effect of tamoxifen on the proliferation of the ER (estrogen receptor)-positive MCF-7, ZR75, T47D human breast cancer cells in vitro. This combination regimen was also more potent than either agent alone at increasing cell apoptosis. In animal experiments, mice treated with both green tea and tamoxifen had the smallest MCF-7 xenograft tumor size, and the highest levels of apoptosis in tumor tissue, as compared with either agent administered alone. Moreover, the suppression of angiogenesis in vivo correlated with larger areas of necrosis and lower tumor blood vessel density in treated xenografts. Green tea decreased levels of ER-
in tumors both in vitro and in vivo. We also observed that green tea blocked ER-dependent transcription, as well as estradiol-induced phosphorylation and nuclear localization of mitogen-activated protein kinase. To our knowledge, this study is the first to show the interaction of green tea with the ER pathway, as well as provide mechanistic evidence that the combination of green tea and tamoxifen is more potent than either agent alone in suppressing breast cancer growth. These results may lead to future improvements in breast cancer treatment and prevention.
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