Journal article
Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells
Molecular nutrition & food research, Vol.55(7), pp.999-1009
07/2011
Handle:
https://hdl.handle.net/2376/105422
PMCID: PMC3129466
PMID: 21374800
Abstract
Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables such as broccoli. The ability of SFN to inhibit histone deacetylase enzymes may be one mechanism by which it acts as a chemoprevention agent. The ability of a chemopreventive agent to specifically cause cytotoxicity in cancer, not normal cells is an important factor in determining its safety and clinical relevance. We characterized the effects of SFN in normal (PrEC), benign hyperplasia (BPH1) and cancerous (LnCap and PC3) prostate epithelial cells. We observed that 15 µM SFN selectively induced cell cycle arrest and apoptosis in BPH1, LnCap and PC3 cells but not PrEC cells. SFN treatment also selectively decreased HDAC activity, and Class I and II HDAC proteins, increased acetylated histone H3 at the promoter for
P21
, induced p21 expression and increased tubulin acetylation in prostate cancer cells. HDAC6 over-expression was able to reverse SFN-induced cyotoxicity. In PrEC cells, SFN caused only a transient reduction in HDAC activity with no change in any other endpoints tested. The differences in sensitivity to SFN in PrEC and PC3 are likely not due to differences in SFN metabolism or differences in phase 2 enzyme induction. From these data we conclude that SFN exerts differential effects on cell proliferation, HDAC activity and downstream targets in normal and cancer cells.
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Details
- Title
- Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells
- Creators
- John D Clarke - Molecular and Cellular Biology Program, Oregon State University, Corvallis, OR 97331Anna Hsu - Department of Nutrition and Exercise Sciences, Oregon State University, Corvallis, OR 97331Zhen Yu - Department of Nutrition and Exercise Sciences, Oregon State University, Corvallis, OR 97331Roderick H Dashwood - Linus Pauling Institute, Oregon State University, Corvallis, OR 97331Emily Ho - Department of Nutrition and Exercise Sciences, Oregon State University, Corvallis, OR 97331
- Publication Details
- Molecular nutrition & food research, Vol.55(7), pp.999-1009
- Academic Unit
- Pharmaceutical Sciences, Department of
- Grant note
- R01 CA122906-01A1 || CA / National Cancer Institute : NCI
- Identifiers
- 99900546898501842
- Language
- English
- Resource Type
- Journal article