P02.09.B Valproic acid changes total DNA methylation level and influences temozolomide effect in glioblastoma cell lines

Abstract Background Valproic acid (VPA) is a first-line antiepileptic drug for glioblastoma (GBM) patients. There also some evidence it improves the clinical outcome in those However, exact mechanism of VPA action vague. Temozolomide (TMZ) chemotherapeutic GBM. Epigenetics offers connection between genetic and environmental factors that influence development disease. The best-characterized epigenetic mark 5-methylcytosine (m5C) DNA. aim project to show effects administration on total DNA methylation level. Material Methods Using nucleotide post-labeling method, we analyzed amount m5C GBM (T98G, U118, U138), cancer (HeLa) normal (HaCaT) cell lines treated with VPA, combination TMZ. Results We adjusted doses ones achieved central nervous system during treatment. observed dose-dependent changes neoplastic lack such effect line. alone produced clear increase scarce non-neoplastic In lines, TMZ decreased level m5C. exposition cells caused an adverse synergistic resulting demethylation. highest loss was at concentration (100 μM) (350 μM), after 3 h incubation T98G Conclusion Total glioma under treatment suggest new promote implications adjusting therapy Our results potential possible obstacles combined VPA. experiments both drugs leads hypomethylation. Therefore conclusion would be stop chemotherapy temporarily.