The Effects of Apoptosis and the Cell Cycle Arresting of Valproate and Nicotinamide on U87 Cell Line

Epigenetic changes such as histone acetylation changes affecting genes play an important role in the development of various human cancers. HDAC inhibitors are now approved by the FDA for the treatment of cancer malignancies as well as clinical trials for tumors. Histone deacetylases play a role in the onset and progression of many cancers through effects on cell cycle, epithelial differentiation and apoptosis. We examined the antiproliferative effects of valproate with a combination of nicotinamide in human glioblastoma U87 cell line. The MTT assay showed that valproate at 0.5 mM, when used alone weakly, suppressed proliferation of cells (39%±3.05) and combination treatment of valproate + nicotinamide strongly suppressed cell proliferation (60%±3.5). Flow cytometric analysis showed that in the treatment of cells when the combination of valproate and nicotinamide was used, it showed more inhibitory effects on cell viability than when valproate alone was used. Also, western blot analyses have done to study the acetyl-histone H3 levels, and quantitative Real time PCR were performed on expression of p21 gene in U87 cell line. The combination treatment of valproate + nicotinamide enhanced the expression of p21 gene. The biological response of the cell line correlated with the increase of histone H3 acetylation after nicotinamide and valproate application. The findings indicate that co-administration of valproate and nicotinamide can have inhibitory effects on the growth and proliferation of human glioblastoma U-87 cells and may be a suitable option for new treatments for brain tumors. Key words: U87 cell, HDAC, HAT, Valproate, Nicotinamide