The effect of sulforaphane on histone deacetylase activity in keratinocytes: Differences between in vitro and in vivo analyses

Sally E Dickinson, Jadrian J. Rusche, Sergiu L. Bec, David J. Horn, Jaroslav Janda, So Hyun Rim, Catharine Smith, G. Timothy Bowden

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Sulforaphane is a natural product found in broccoli, which is known to exert many different molecular effects in the cell, including inhibition of histone deacetylase (HDAC) enzymes. Here, we examine for the first time the potential for sulforaphane to inhibit HDACs in HaCaT keratinocytes and compare our results with those found using HCT116 colon cancer cells. Significant inhibition of HDAC activity in HCT116 nuclear extracts required prolonged exposure to sulforaphane in the presence of serum. Under the same conditions HaCaT nuclear extracts did not exhibit reduced HDAC activity with sulforaphane treatment. Both cell types displayed down-regulation of HDAC protein levels by sulforaphane treatment. Despite these reductions in HDAC family member protein levels, acetylation of marker proteins (acetylated Histone H3, H4, and tubulin) was decreased by sulforaphane treatment. Time-course analysis revealed that HDAC6, HDAC3, and acetylated histone H3 protein levels are significantly inhibited as early as 6h into sulforaphane treatment. Transcript levels of HDAC6 are also suppressed after 48h of treatment. These results suggest that HDAC activity noted in nuclear extracts is not always translated as expected to target protein acetylation patterns, despite dramatic inhibition of some HDAC protein levels. In addition, our data suggest that keratinocytes are at least partially resistant to the nuclear HDAC inhibitory effects of sulforaphane, which is exhibited in HCT116 and other cells.

Original languageEnglish (US)
Pages (from-to)1513-1520
Number of pages8
JournalMolecular Carcinogenesis
Volume54
Issue number11
DOIs
StatePublished - Nov 1 2015

Keywords

  • Chemoprevention
  • Isothiocyanate
  • Skin

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

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