Modulation of Androgen-Induced Oxidative Stress Responses as a Chemopreventive Measure in Prostate Cancer
Abstract
Changes in cellular redox status are believed to be contributing factors to the development of cancer. We have previously reported that physiologic levels of androgens induce the production of reactive oxygen species in the androgen-responsive LNCaP prostate carcinoma cell line. We hypothesize that androgen-induced changes in prostate redox status may contribute to prostate carcinogenesis. Chemopreventive measures may reduce the development of prostate cancer. This study addresses several molecular mechanisms that have been implicated in cellular redox status changes including cellular calcium homeostasis, redox-sensitive transcription factor activation, nitric oxide generation, and the role of redox-sensitive apoptotic factors. Calcium homeostasis studies are currently in progress. Activity of the redox sensitive transcription factor NF-KB was found to be induced by androgen exposure in LNCaP cells, but not in the androgen-independent DU-145 cell line. Inhibition of nitric oxide synthase activity did not change the production of androgen-induced reactive oxygen species in LNCaP cells. Therefore, nitric oxide is an unlikely mediator of androgen-induced oxidative stress in LNCaP cells. The antiapoptotic Bcl-2 whole cell protein levels were decreased by exposure to 1 nM Rl 881 and 20 micronM a-tocopherol succinate whereas mitochondrial Bcl-2 protein levels were found to be increased under these conditions. The mitochondrial Bax protein levels were found to be decreased by exposure to 1 nM Rl881 and 20 %MICRONM a-tocopherol succinate. These results may provide valuable information for pathways to investigate as targets for chemopreventive measures in prostate carcinogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADB264578
Entities
People
- Todd A. Thompson
Organizations
- University of Wisconsin–Madison