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 BI/cdkl 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 BI protein and the ability of 2-ME to increase apoptosis in prostate cancer cells; 2) overexpression of cyclin BI increases 2-ME-mediated apoptosis while inhibition of cdkl activity lowers 2-ME-mediated apoptosis; 3)10w doses of 2-ME and docetaxel can increase G2/M cell cycle arrest and apoptosis in prostate cancer cell lines and in the GyIT 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 BI prntein which is minimally expressed in normal cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2007
- Accession Number
- ADA472868
Entities
People
- Carlos Perez-stable
Organizations
- University of Miami