STEM-07EXPOSING GLIOBLASTOMA STEM CELLS TO LEVETIRACETAM RESULTS IN AN ALTERED MOLECULAR PROGRAM

Abstract

Glioblastoma stem cells (GSCs) are widely accepted as key players in glioblastoma (GBM) pathogenesis. Levetiracetam is extensively used for both prevention and therapy of seizures in GBM and also reported to inhibit glioma cell proliferation. However, its global impact on expression profiles specifically in GSC is unknown. The purpose of this research was to evaluate the impact of Levetiracetam on the expression profiles and cellular properties of GSCs. Total RNA from two independent GSC lines after Levetiracetam exposure was used for mRNA and miRNA expression profiling by microarrays. Gene ontology (GO) and ingenuity pathway analyses (IPA) of differentially expressed genes including miRNAs were used to uncover altered pathways. Additionally, the impact of Levetiracetam on cellular properties such as self-renewal (limiting dilution assay), differentiation (neural lineage marker analysis), proliferation (BrdU labeling), and invasion (Boyden chamber assays) was studied. Exposure to Levetiracetam altered expression profiles of GSCs. Gene ontology (GO) and ingenuity pathway analyses (IPA) of significantly altered genes in Levetiracetam treated cells show multiple cellular functions being potentially affected. Further, in vitro experiments such as self-renewal, differentiation, proliferation and migration/invasion assays indeed showed a significant impact on cellular behavior upon treatment of GSCs with Levetiracetam. In this pre-clinical study we uncovered the impact of Levetiracetam on the expression profiles of GSC, which alters the behavior of GSCs. These molecular findings bare potential to significantly impact GBM patient care by optimizing the established therapy with Levetiracetam.