Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells
Clarke JD, Hsu A, Yu Z, Dashwood RH, Ho E
Molecular nutrition & food research · 142 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- Cells or lab samples
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Government
- National Cancer Institute
- Government
- National Institute of Environmental Health Sciences
- Government
- National Center for Research Resources
- Government
- NIH
- Industry group
- Oregon AES
- Government
- NCI NIH HHS
- Government
- NCRR NIH HHS
- University or hospital
- Environmental Health Science Center at Oregon State University
- Government
- NIEHS NIH HHS
- Grants
- National Cancer Institute (R01 CA-122906); National Cancer Institute (CA 090890); National Institute of Environmental Health Sciences (P30ES000210); National Institute of Environmental Health Sciences (#P30-ES00210); National Center for Research Resources (S10 RR022589); National Cancer Institute (P01 CA090890); National Center for Research Resources (1S10RR022589); National Cancer Institute (CA122906)
Based on 9 listed funder(s).
Publication
- Published
- 2011-03-04 · Mol Nutr Food Res · vol. 55 · issue 7 · pp. 999–1009
- Publisher
- Wiley
- Cited
- 178 citations · more than 97% of similar papers · 5.6× the field average
- Impact
- Top 10% most cited in its field
- References
- 38 works
- Access
- Open access (repository copy)
- Research areas
- Genomics, phytochemicals, and oxidative stress · Garlic and Onion Studies · Histone Deacetylase Inhibitors Research
- Keywords
- Sulforaphane, LNCaP, Cancer research, Prostate cancer, Apoptosis, Acetylation, Histone deacetylase, Cell cycle, Chemistry, Cancer cell, Cell cycle checkpoint, Cancer, Biology, Histone, Internal medicine, Medicine, Biochemistry
- MeSH
- prostate, cell line, cell line, tumor, cytosol, epithelial cells, humans, prostatic neoplasms, hyperplasia, thiocyanates, isothiocyanates, sulfoxides, tubulin, histone deacetylases, nad(p)h dehydrogenase (quinone), histones, anticarcinogenic agents, cell cycle, apoptosis, acetylation, male, cyclin-dependent kinase inhibitor p21, promoter regions, genetic, histone deacetylase 2, histone deacetylase inhibitors, histone deacetylase 6, histone deacetylase 3
5 authors
From US
- John ClarkeOregon State University
- Anna J. C. HsuOregon State University
- Zhen YuOregon State University
- Roderick H. DashwoodOregon State University
- Emily H. Ho · correspondingOregon State University
Abstract
Scope
Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables such as broccoli. The ability of SFN to inhibit histone deacetylase (HDAC) 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 and not normal cells is an important factor in determining its safety and clinical relevance.
Methods and results
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.
Conclusion
SFN exerts differential effects on cell proliferation, HDAC activity and downstream targets in normal and cancer cells.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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