2-Methoxyestradiol as a Chemotherapeutic for Prostate Cancer
Abstract
2-Methoxyestradiol (2-ME) is an endogenous metabolite of estradiol with promise for cancer chemotherapy. 2-ME can arrest mitosis and induce apoptosis in a wide variety of cancer cells, including androgen-independent prostate cancer. To better understand its anti-prostate cancer action, we have focused on events related to mitotic cell cycle arrest (G2/M) and induction of apoptosis in LNCaP, DU 145, and PC-3 human prostate cancer cell lines. Treatment with 2-ME for 24 h increased cyclin Bl protein and its associated kinase (cdkl) activity followed by later induction of apoptosis at 48 and 72 h. Cyclin-dependent kinase inhibitors alsterpaullone and purvalanol A prevented 2-ME-mediated increase in cyclin Bl-dependent kinase activity and induction of apoptosis. Decrease in cyclin Bl- and cyclin A-dependent kinase activity occurred at later times when apoptosis was increased. It is likely, however, that the higher levels of the anti-apoptotic proteins Bcl-xL and survivin in DU 145 and PC-3 compared to LNCaP accounts for the differential induction of apoptosis by 2-ME (LNCaP > DU 145 > PC-3). Our results suggest a common mechanism of 2-ME inhibition of the different types of prostate cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA427139
Entities
People
- Carols Perez-stable
Organizations
- University of Miami