Accession Number:

ADB281679

Title:

Modulation of Androgen-Induced Oxidative Stress Responses as a Chemopreventive Measure in Prostate Cancer

Descriptive Note:

Annual rept. 16 Aug 1999-15 Aug 2001

Corporate Author:

WISCONSIN UNIV-MADISON

Personal Author(s):

Report Date:

2001-09-01

Pagination or Media Count:

24.0

Abstract:

We have previously reported that androgens induce oxidative stress 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 implicated in cellular redox status. Intracellular calcium levels were increased by androgen exposure, which could be inhibited by vitamin E treatment. Activity of the redox sensitive transcription factors AP-1 and NF-kB were induced by androgen exposure in LNCaP cells, but not in the androgen-independent DU-145 cell line. AP-1 activity was also increased by vitamin E exposure in LNCaP and DU-145 cells. Nitric oxide production was found to be 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 R1881 and 20 Micron-M alpha-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 R1881 and 20 Micron-M alpha-tocopherol succinate. These results may provide valuable information for pathways to investigate as targets for chemopreventive measures in prostate carcinogenesis.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research
  • Stress Physiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE