Diet and Epigenetic Interactions in Prostate Cancer Prevention
Abstract
The central hypothesis for this research project is that sulforaphane acts as an HDAC and DNMT1 inhibitor in the prostate, causing enhanced histone acetylation and DNA demethylation at specific promoters, and induction of cell cycle arrest/apoptosis in cancer cells, leading to cancer prevention. To test this hypothesis we characterized the effects of SFN in normal (PrEC), benign hyperplasia (BPH1) and cancerous (LnCap and PC3) prostate epithelial cells. We observed that SFN selectively induced cell cycle arrest and apoptosis in BPH1, LnCap and PC3 cells but not PrEC cells. SFN treatment also decreased HDAC activity, decreased specific HDAC proteins, increased acetylated histone H3 at the promoter for P21, induced p21 expression and increased tubulin acetylation. In PrEC cells, SFN caused only a transient reduction in HDAC activity with no change in any other endpoints tested. From these data we conclude that SFN exerts differential effects on HDAC activity and downstream targets in normal and cancer cells. We have also employed a rodent model of prostate cancer to determine the effects of SFN on the epigenetic endpoints mentioned above. Histopathology analysis revealed that SFN reduced the severity of prostate cancer in this rodent model.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2011
- Accession Number
- ADA548139
Entities
People
- John Clarke
Organizations
- Oregon State University