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2-Methoxyestradiol as a Chemotherapeutic for Prostate Cancer
Annual rept. 1 Apr 2005-31 Mar 2006
MIAMI UNIV FL
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2-Methoxyestradiol 2-ME is an endogenous metabolite of estradiol with promise for cancer chemotherapy, including advanced prostate cancer. Our hypothesis is one of the cancer-specific mechanisms whereby 2-ME exerts its anti-prostate cancer activity is the deregulated activation of cyclin B1cdk1 kinase during the cell cycle, which results in the induction of apoptotic cell death. Several experimental results support this hypothesis 1 there is a positive correlation between the levels of cyclin B1 protein and the ability of 2-ME to increase G2M cell cycle arrest and apoptosis in prostate cancer cells 2 inhibition of cdk1 activity lowers 2-ME-mediated apoptosis while overexpression of cyclin B1 increases 2-ME-mediated apoptosis 3 low doses of 2-ME and docetaxel can increase G2M cell cycle arrest and apoptosis in prostate cancer cell lines and in the G T transgenic mouse model of prostate cancer greater than either drug alone. We conclude that 2-ME can increase apoptosis in prostate cancer cells because of the expression of cyclin B1 protein, which is minimally expressed in normal cells.
APPROVED FOR PUBLIC RELEASE