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

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1127-1133
Number of pages7
JournalOral Oncology
Volume47
Issue number12
DOIs
Publication statusPublished - Dec 2011
Externally publishedYes

Fingerprint

Histone Deacetylase Inhibitors
Squamous Cell Carcinoma
Cyclin-Dependent Kinase 6
Foster Home Care
Cyclin D1
Acetylation
Caspases
Heterografts
Epigenomics
Nude Mice
Histones
Reactive Oxygen Species
Neoplasms
Cell Survival
Cell Cycle
Down-Regulation
Tumor Necrosis Factor-alpha
Apoptosis
Gene Expression
Cell Line

Keywords

  • (S)-HDAC42
  • Akt
  • Histone deacetylase inhibitor
  • NF-κB
  • Oral cancer

ASJC Scopus subject areas

  • Oncology
  • Oral Surgery
  • Cancer Research

Cite this

Antitumor activity of a novel histone deacetylase inhibitor (S)-HDAC42 in oral squamous cell carcinoma. / Bai, Li Yuan; Chiu, Chang Fang; Pan, Shiow Lin; Sargeant, Aaron M.; Shieh, Tzong Ming; Wang, Ying Chu; Weng, Jing Ru.

In: Oral Oncology, Vol. 47, No. 12, 12.2011, p. 1127-1133.

Research output: Contribution to journalArticle

Bai, Li Yuan ; Chiu, Chang Fang ; Pan, Shiow Lin ; Sargeant, Aaron M. ; Shieh, Tzong Ming ; Wang, Ying Chu ; Weng, Jing Ru. / Antitumor activity of a novel histone deacetylase inhibitor (S)-HDAC42 in oral squamous cell carcinoma. In: Oral Oncology. 2011 ; Vol. 47, No. 12. pp. 1127-1133.
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