Abstract 402: Tumor necrosis factor-alpha and apoptosis induction in melanoma cells through histones modification by 3-deazaneplanocin A

Abstract

Abstract Tumor necrosis factor-alpha (TNFα) is cytokine, which influences the tumor microenvironment. While melanoma is known to express variable levels of TNFα, its regulation is not well understood. The objective of the study was to investigate the epigenetic regulation of TNFα in melanoma cells. Melanoma cell lines were treated with 3-Deazaneplanocin A(DZNep), an inhibitor of polycomb-repressive complex 2(PRC2), and analyzed for its effect on the cell viability assay and apoptosis assay. PRC2 and histones H3K27me3, H3K4me2 and H3K9ac activity were assessed pre- and post-DZNep by Western blot on cell lines and tumors. ChIP-qPCR array, chromatin immunoprecipitation, and PCR array analysis of melanoma lines treated with DZNep. DZNep could induce apoptosis in melanoma cells, and up-regulate TNFα expression. Specific histones were associated with the upregulation of TNFα expression by ChIP-qPCR array. The repressive histone mark, H3K27me3, as well as the active histone marks, H3K4me2 and H3K9ac, were correlated with the regulation of TNFα expression. We demonstrated that DZNep can activate TNFα expression in melanoma through histone modification. These findings suggest that epigenetic agents targeting PRC2 can activate TNFα in melanoma cells. The DNA methylation, H3K27me3, H3K4me2, and H3K9ac modification, contribute to TNFα regulation. Citation Format: Ryo Tanaka, Nicholas Donovan, Qiang Yu, Reiko Irie, Dave S.B. Hoon. Tumor necrosis factor-alpha and apoptosis induction in melanoma cells through histones modification by 3-deazaneplanocin A. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 402. doi:10.1158/1538-7445.AM2014-402