Prostate Cancer Prevention Through Induction of Phase 2 Enzymes
Abstract
Virtually all human prostate cancers harbor a common somatically acquired genetic lesion - loss of expression of the carcinogen defense enzyme glutathione S-transferase-pi (GST-pi) due to methylation of deoxycytidine residues in the promoter region of the gene. We have hypothesized that this lesion, acquired early in prostate carcinogenesis, renders prostate cells susceptible to accumulating genetic damage and ultimately to frank carcinoma. We propose to investigate whether a suitable prostate cancer preventive strategy could involve up-regulation of global carcinogen defenses (phase 2 enzymes) by chemical or dietary means. Over the past year, we have made extraordinary progress in developing this hypothesis. We have identified sulforaphane, a dietary isothiocyanate found in cucifers, as the most potent phase 2 enzyme inducing agent in human prostate cancer cell lines compared to over 50 other compounds screened in our laboratory. Sulforaphane readily induced increased expression of quinone reductase, GST-alpha, and gamma glutamylcysteine synthase, the rate limiting enzyme in glutathione synthetic pathways.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA385367
Entities
People
- James D Brooks
Organizations
- Stanford University