Antitumor activity of a novel histone deacetylase inhibitor (S)-HDAC42 in oral squamous cell carcinoma

Li Yuan Bai, Chang Fang Chiu, Shiow Lin Pan, Aaron M. Sargeant, Tzong Ming Shieh, Ying Chu Wang, Jing Ru Weng

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8 引文 斯高帕斯(Scopus)

摘要

The aberrant regulation of epigenetic systems including histone acetylation contributes to inappropriate gene expression in cancer cells. In this study, we investigated the antitumor effects of the novel histone deacetylase inhibitor (S)-HDAC42 in oral squamous cell carcinoma (OSCC) cells. The antiproliferative effect of (S)-HDAC42 was multifold higher than that of suberoylanilide hydroxamic acid in a panel of oral squamous carcinoma cell lines examined. (S)-HDAC42 mediated caspase-dependent apoptosis by targeting multiple signaling pathways relevant to cell cycle progression and survival. We demonstrated that (S)-HDAC42 downregulated the levels of phospho-Akt, cyclin D1, and cyclin-dependent kinase 6, accompanied by increased p27 and p21 expression. In addition, (S)-HDAC42 suppressed NF-κB signaling by blocking tumor necrosis factor-α-induced nuclear translocation, and activated reactive oxygen species generation. Finally, (S)-HDAC42 exhibited high potency in suppressing OSCC tumor growth in a Ca922 xenograft nude mouse model. Together, these findings underscore the translational value of (S)-HDAC42 in fostering new therapeutic strategies for OSCC.
原文英語
頁(從 - 到)1127-1133
頁數7
期刊Oral Oncology
47
發行號12
DOIs
出版狀態已發佈 - 十二月 2011
對外發佈

ASJC Scopus subject areas

  • 腫瘤科
  • 口腔外科
  • 癌症研究

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