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-alpha 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.