title: The effect of sulforaphane on histone deacetylase activity in keratinocytes: Differences between in vitro and in vivo analyses.
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 6 h into sulforaphane treatment. Transcript levels of HDAC6 are also suppressed after 48 h 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.
authors.affiliation: The University of Arizona Cancer Center, The University of Arizona, Tucson, Arizona.|Department of Pharmacology, The University of Arizona, Tucson, Arizona.
authors.forename: Sally E
authors.initials: SE
authors.lastname: Dickinson
authors.affiliation: The University of Arizona Cancer Center, The University of Arizona, Tucson, Arizona.
authors.forename: Jadrian J
authors.initials: JJ
authors.lastname: Rusche
authors.affiliation: The University of Arizona Cancer Center, The University of Arizona, Tucson, Arizona.
authors.forename: Sergiu L
authors.initials: SL
authors.lastname: Bec
authors.affiliation: The University of Arizona Cancer Center, The University of Arizona, Tucson, Arizona.
authors.forename: David J
authors.initials: DJ
authors.lastname: Horn
authors.affiliation: The University of Arizona Cancer Center, The University of Arizona, Tucson, Arizona.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Janda
authors.affiliation: The University of Arizona Cancer Center, The University of Arizona, Tucson, Arizona.
authors.forename: So Hyun
authors.initials: SH
authors.lastname: Rim
authors.affiliation: Department of Pharmacology and Toxicology, The University of Arizona, Tucson, Arizona.
authors.forename: Catharine L
authors.initials: CL
authors.lastname: Smith
authors.affiliation: The University of Arizona Cancer Center, The University of Arizona, Tucson, Arizona.|Department of Cellular and Molecular Medicine, The University of Arizona, Tucson, Arizona.
authors.forename: G Timothy
authors.initials: GT
authors.lastname: Bowden
mesh_terms: D000107:Acetylation / Q000187:drug effects; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D045325:HCT116 Cells; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D013454:Sulfoxides; D000099186:Histone Deacetylase 3
chemical_list: D016588:Anticarcinogenic Agents; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006657:Histones; D017879:Isothiocyanates; D013454:Sulfoxides; D000099186:Histone Deacetylase 3; C433811:HDAC6 protein, human; C016766:sulforaphane
keywords: chemoprevention; isothiocyanate; skin