Understanding Molecular Mechanisms of Androgen-Induced Oxidative Stress for Chemoprevention of Prostate Cancer
Abstract
The goal of this project was to identify factors that contribute to and consequences of androgen-induced oxidative stress in human prostate carcinoma cells. The JunD transcription factor was found to play a key role in androgen induced oxidative stress. Activation of oxidative stress by androgen was found to produce significant levels of cellular damage. This finding supports our hypothesis that androgen may contribute to prostate carcinogenesis through the development of oxidative stress. Antioxidant enzyme activities were significantly altered by androgen-induced stress and vitamin E treatment. Interestingly, we found that the combination of androgen and vitamin E succinate potentiated LNCaP cell death, which may have important implications for prostate cancer prevention and therapy. In our search for alternative antioxidants, we discovered that the antioxidant moiety of vitamin E is a potent inhibitor of androgenic activity. We have also discovered that oxidative stress produced by androgen exposure is not a simple manifestation of androgen receptor activation. Therefore, multiple factors contribute to androgen-induced oxidative stress and we are currently trying to identify these factors. All of the tasks performed in this project led to a much greater understanding of the mechanism and consequences of androgen to produce oxidative stress in prostate cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2005
- Accession Number
- ADA433860
Entities
People
- George Wilding
Organizations
- University of Wisconsin–Madison