Abstract
Abstract Background: Neuroblastoma (NB), a childhood neoplasm arising from neural crest cells, is characterized by a diversity of clinical behaviors ranging from spontaneous remission to rapid tumor progression and death. In addition to genetic abnormalities, recent studies have indicated that epigenetic aberrations also contribute to NB pathogenesis. However, the epigenetic mechanisms underlying the pathogenesis of NB are largely unknown. Methods: Cell proliferation was measured by cell counting and BrdU incorporation assay in a human NB cell line (LA1-55n). Expression of MYCN was measured by real-time PCR. Caspase 3/7 activity was measured by Caspase-Glo 3/7 assay kit. The level of global DNA methylation was measured by liquid chromatography-mass spectroscopy. Results: BIX-01294, a specific inhibitor of EHMT2 (a key enzyme for histone H3 dimethylation at lysine-9), decreased proliferation of NB LA1-55n cells and induced apoptosis via increasing caspase 3 activity. BIX-01294 at a concentration of 1µg/ml inhibited NB cell proliferation, decreased expression of the MYCN oncogene, and increased global DNA methylation levels. At a concentration of 5 µg/ml and 10 µg/ml, BIX-01294 significantly increased caspase 3/7 activity. Conclusion: Our results demonstrate that histone lysine methylation is involved in cell proliferation, apoptosis, and global DNA methylation in human NB cells. Further understanding of this mechanism may provide insight into the pathogenesis of NB progression and lead to novel treatment strategies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1037. doi:1538-7445.AM2012-1037
Published Version
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