title: The in vitro apoptotic effects of A248 and A1659, newly synthetic histone deacetylase inhibitors in oral cancer cells.
abstract: OBJECTIVE
  Histone deacetylase (HDAC) inhibitors represent potential therapeutic agents against various cancers. In this study, we attempt to identify whether newly synthesized HDAC inhibitors, A248 and A1659, can be effective anti-cancer drug candidates for oral cancer.
  
  
  METHODS
  The anti-cancer activities of A248 and A1659 in MC-3 and HN22 human oral cancer cells were evaluated by 3-(4,5-dimethylthiazol-20yl)-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium (MTS) assay, 4'-6-diamidino-2-phenylindole (DAPI) staining, Western blot analysis, immunocytochemistry, and small interference RNA (siRNA) technology.
  
  
  RESULTS
  A248 and A1659 enhanced histone acetylation and decreased the viability of MC-3 and HN22 cells. A248 and A1659 also induced apoptosis, as evidenced by altered nuclear features and poly(ADP-ribose)polymerase (PARP) cleavage. A248 and A1659 markedly decreased Sp1 expression in a concentration- or time-dependent manner and blocked nuclear translocation of Sp1 protein from the cytosol, which contributed to an increase in p27 expression and a decrease in cyclin D1 expression. Furthermore, the knockdown of Sp1 protein with siRNA caused marked alteration of p27 and cyclin D1 expression to induce apoptosis. The most popular HDAC inhibitor, trichostatin A (TSA) also induced apoptosis and reduced the expression level of Sp1 protein.
  
  
  CONCLUSIONS
  These results suggest that A248 and A1659, two new HDAC inhibitors, may be attractive therapeutic drug candidates for targeting Sp1 in human oral cancer cells.
authors.affiliation: Department of Oral Pathology, School of Dentistry, Institute of Oral Bioscience, Chonbuk National University, Jeonju, Korea.
authors.forename: J-A
authors.initials: JA
authors.lastname: Shin
authors.forename: G
authors.initials: G
authors.lastname: Han
authors.forename: S-K
authors.initials: SK
authors.lastname: Park
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.forename: H-J
authors.initials: HJ
authors.lastname: Kim
authors.forename: S-D
authors.initials: SD
authors.lastname: Cho
authors.forename: H M
authors.initials: HM
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D051379:Mice; D009062:Mouth Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D056572:Histone Deacetylase Inhibitors
keywords: A1659; A248; apoptosis; histone deacetylase inhibitor; oral cancer; specificity protein 1