title: [Modulation of histone acetylation and induction of apoptosis in SMMC-7721 cells by phenylhexyl isothiocyanate].
abstract: OBJECTIVE
  To investigate the effect of phenylhexyl isothiocyanate (PHI) on histone acetylation and apoptosis in hepatocellular carcinoma cell line (SMMC-7721) in vitro.
  
  
  METHODS
  The viability of SMMC-7721 cells was determined by trypan blue exclusion. Apoptotic cells were assessed by TUNEL assay. The proteins of Bcl-2, Procaspase-9, Procaspase-8, Procaspase-3, caspase-9, caspase-3, histone acetylated H3 and H4 were detected by Western blot.
  
  
  RESULTS
  Compared with the vehicle control, PHI at 5, 10, 20, 40 and 80 µmol/L reduced the cell viability of SMMC-7721 cells in a concentration-dependent manner. PHI induced apoptosis in SMMC-7721 cells. An increased amount of apoptotic cells was detected after 7 hours exposure to PHI at 10, 20, and 40 µmol/L, 6.9% ± 2.4%, 17.5% ± 4.2% and 54.5% ± 5.4%, respectively, while that of the vehicle control was 4.5% ± 2.3% (P < 0.05). Along with the prolongation of time and increase of dose, the expressions of bcl-2, procaspase-9, procaspase-3 were decreased, that of caspase-9 and caspase-3 was increased. In contrast, alteration of procaspase-8 was not significant at those concentrations. PHI accumulated acetylated histone H3 and H4. After 3 hours exposure to PHI at 10, 20 and 40 µmol/L, the level of histone acetylated H3 was 1.87-, 2.43-, 3.67-fold increased and histone acetylated H4 was 1.29-, 1.45-, and 2.25-fold increased, compared with that of the vehicle control. The protein of histone acetylated H3 and H4 was significantly accumulated after 7 hours exposure.
  
  
  CONCLUSIONS
  PHI is a new histone deacetylation inhibitor. It may induce accumulation of histone acetylation H3 and H4, inhibit cell growth and induce apoptosis in SMMC-7721 cells via the mitochondrial pathway.
authors.affiliation: Department of Gastroenterology, Affiliated Zhangzhou Hospital of Fujian Medical University, Zhangzhou 363000, China.
authors.forename: Ya-dong
authors.initials: YD
authors.lastname: Lai
authors.forename: Xu-dong
authors.initials: XD
authors.lastname: Ma
authors.forename: Yi-qun
authors.initials: YQ
authors.lastname: Huang
authors.forename: Xiang-nong
authors.initials: XN
authors.lastname: Xu
authors.forename: Xiao-zhong
authors.initials: XZ
authors.lastname: Wang
authors.forename: Dicky J W
authors.initials: DJ
authors.lastname: Chiao
authors.forename: Delong
authors.initials: D
authors.lastname: Liu
mesh_terms: D000107:Acetylation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D017879:Isothiocyanates / Q000008:administration & dosage / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D017879:Isothiocyanates; D019253:Proto-Oncogene Proteins c-bcl-2; C073279:6-phenylhexyl isothiocyanate; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9