Abstract
Abstract Background: The polycomb group gene, EZH2, mediates the histone methyltransferase activity, and functions as transcriptional repressor involved in gene silencing. It is involved in the malignant transformation and biological aggressiveness of several human cancers. We have previously shown that high EZH2 expression is correlated with tumor aggressiveness and is an independent unfavorable prognostic factor in non-small cell lung cancers (NSCLCs). However, the role of EZH2 in lung cancer cells has not been fully determined. Methods: In the present study, we evaluated the effect of a histone methyltransferase EZH2 inhibitor, 3-Deazaneplanocin A (DZNep), in NSCLC cell lines. Results: DZNep depleted cellular levels of EZH2 and SUZ12, and inhibited histone H3 lysine 27 trimethylation. DZNep inhibited proliferation of NSCLC cells dose- dependently through apoptosis and G1 cell cycle arrest which was partially associated with cyclin A decrease and p27Kip1 accumulation. Conclusion: Epigenetic therapy with the histone methyltransferase EZH2 inhibitor DZNep may constitute a novel approach for NSCLCs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2011. doi:10.1158/1538-7445.AM2011-2011
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