2-Methoxyestradiol as a Chemotherapeutic for Prostate Cancer
Abstract
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 B1/cdk1 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 G2/M 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 G2/M 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2006
- Accession Number
- ADA455889
Entities
People
- Carlos Perez-stable
Organizations
- University of Miami