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

Abstract

Glioblastomas (GBM), also known as glioblastoma multiforme, are the most aggressive type of brain cancer. Currently, there is no effective treatment for GBM, highlighting the pressing need for new therapeutic strategies. In a recent study, we demonstrated that specific combinations of epigenetic modifiers significantly affect the metabolism and proliferation rate of the two most aggressive GBM cell lines, D54 and U-87. Importantly, these combinations exhibited minimal effects on the growth of normal stem cells. In this study, we extended our investigation to include a patient-derived GBM stem cell line. Our results showed that the combinations of modulators of histone and DNA covalent modifying enzymes that synergistically suppress D54 and U87 cell line growth also impair the viability of the patient-derived GBM stem cell line. These findings suggest that epigenetic modifiers alone or in specific combinations exhibit a cytotoxic effect on established and low-passage patient-derived GBM cell lines, and thus could be a promising therapeutic approach for this type of brain cancer.