Research Article

Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells

  1. John D. Clarke1,2,
  2. Anna Hsu2,
  3. Zhen Yu2,
  4. Roderick H. Dashwood3,4,
  5. Emily Ho2,3,*

Article first published online: 4 MAR 2011

DOI: 10.1002/mnfr.201000547

Issue

Molecular Nutrition & Food Research

Molecular Nutrition & Food Research

Volume 55, Issue 7, pages 999–1009, July 2011

Additional Information

How to Cite

Clarke, J. D., Hsu, A., Yu, Z., Dashwood, R. H. and Ho, E. (2011), Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells. Mol. Nutr. Food Res., 55: 999–1009. doi: 10.1002/mnfr.201000547

Author Information

  1. 1

    Molecular and Cellular Biology Program Oregon State University, Corvallis, OR, USA

  2. 2

    Department of Nutrition and Exercise Sciences Oregon State University, Corvallis, OR, USA

  3. 3

    Linus Pauling Institute, Oregon State University, Corvallis, OR, USA

  4. 4

    Department of Environmental and Molecular Toxicology Oregon State University, Corvallis, OR, USA

*117 Milam Hall, Oregon State University, Corvallis, OR 97331, USA Fax: +1-541-737-6914

Publication History

  1. Issue published online: 4 JUL 2011
  2. Article first published online: 4 MAR 2011
  3. Manuscript Accepted: 22 DEC 2010
  4. Manuscript Revised: 14 DEC 2010
  5. Manuscript Received: 2 NOV 2010

Funded by

  • NIH. Grant Numbers: CA090890, CA122906
  • Oregon AES. Grant Numbers: OR00735, 1S10RR022589
  • Environmental Health Science Center at Oregon State University. Grant Number: NIEHS P30 ES00210

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Keywords:

  • Apoptosis;
  • Chemoprevention;
  • Epigenetics;
  • Isothiocyanate;
  • Prostate cancer

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.

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