The in vitro apoptotic effects of A248 and A1659, newly synthetic histone deacetylase inhibitors in oral cancer cells

J. A. Shin, G. Han, S. K. Park, K. Lee, H. J. Kim, S. D. Cho, H. M. Kim

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objectives: 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. Materials and 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)482-489
Number of pages8
JournalOral Diseases
Volume20
Issue number5
DOIs
Publication statusPublished - 2014 Jul

All Science Journal Classification (ASJC) codes

  • Otorhinolaryngology
  • Dentistry(all)

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