The histone deacetylase inhibitor, Trichostatin A, induces G2/M phase arrest and apoptosis in YD-10B oral squamous carcinoma cells.
ABSTRACT Histone acetylation is one of the key chromatin modifications that control gene transcription during development and tumorigenesis. Recently, it was reported that the histone deacetylase inhibitor, Trichostatin A (TSA), induces growth arrest and apoptosis in tumors. However, the molecular mechanisms responsible for its antitumor effects are not clear. The purpose of this study was to investigate the effect of TSA on human oral squamous carcinoma cells and to determine the mechanisms underlying the antitumor activity of TSA. MTT assays showed that TSA inhibited cell proliferation in YD-10B cells. TSA also effectively arrested cell cycle progression at the G2/M phase through the up-regulation of p21waf expression, down-regulation of Cyclin B1 and reduction of the inhibitory phophorylation of Cdc2. In addition, mitochondrial membrane destruction was induced by a 48 h TSA treatment. TSA also induced cytochrome c release and proteolytic activation of caspase 3 and caspase 7 in YD-10B cells. Taken together, these observations in YD-10B oral cancer cells reveal the potential value of TSA in inhibiting oral tumor growth.
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ABSTRACT: Dysregulation of gene expression is a frequent occurrence in oral squamous cell carcinoma (OSCC). However, accumulating evidence suggests that in contrast to genetics, epigenetic modifications consisting of aberrant DNA methylation, histone modifications and altered expression of miRNAs induce OSCC tumorigenesis and perhaps play a more central role in the evolution and progression of this disease. The unifying theme among these three epigenetic mechanisms remains the same, which is aberrant regulation of gene expression. In this article, we provide a comprehensive review of the impact of epigenetics on oral tumorigenesis with a systematic report on aberrant DNA methylation, histone modifications and miRNA regulation in the pathogenesis of OSCC. We provide insights into recent studies on the prospect of biomarkers for early detection and indication of disease recurrence, and novel treatment modalities.Future Oncology 11/2012; 8(11):1407-1425. · 3.20 Impact Factor