Epigenetic modifiers either individually or in specific combinations impair viability of patient-derived glioblastoma cell line while exhibiting moderate effect on normal stem cells growth

Abstract

Abstract Glioblastomas (GBM), also known as glioblastoma multiforme, are the most aggressive type of brain cancers. Currently, there is no real treatment for GBM and thus there is a compelling need for new therapeutic strategies for such type of cancers. Recently, we demonstrated that specific combinations of epigenetic modifiers significantly affect the metabolism and proliferation rate of two most aggressive GBM cell lines D54 and U-87. Importantly, these combinations exhibited minimal effect on normal stem cells growth. In this study we demonstrated that the combinations of modulators of histone and DNA covalent modifying enzymes that synergistically suppress D54 and U87 cell lines growth, also impair the viability of a patient freshly-derived GBM stem cell line. These data suggest that epigenetic modifiers alone or in specific combinations exhibit cytotoxic effect on established and low passage patient derived GB cell lines and thus could be a promising therapeutic approach for such type of brain cancers.