Mechanisms for 2‐methoxyestradiol‐induced apoptosis of prostate cancer cells

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Abstract
Prostate and breast carcinomas are sex hormone‐related carcinomas, which are known to be associated with an over‐expression of the proto‐oncogene Bcl‐2. Here, we report that 2‐methoxyestradiol (2‐ME), an endogenous metabolite of estrogen that does not bind to nuclear estrogen receptors, effectively induces apoptosis in Bcl‐2‐expressing human prostate and breast carcinoma cells in vitro and in a rat prostate tumor model in vivo. In several cell lines derived from prostate, breast, liver and colorectal carcinomas, 2‐ME treatment led to an activation of c‐Jun N‐terminal kinase (JNK) and phosphorylation of Bcl‐2, which preceded the induction of apoptosis. In summary, our data suggest that 2‐ME induces apoptosis in epithelial carcinomas by causing phosphorylation of JNK, which appears to be correlated with phosphorylation of Bcl‐2.