DDIS-35. RelA-ACTIVITY IS ESSENTIAL FOR CANNABIDIOL-MEDIATED CYTOTOXICITY IN AN IDENTIFIED SUBSET OF GLIOBLASTOMA. (11th November 2019)

• Record Type: Journal Article
• Authors: Volmar, Marie; Nagl, Bernhard; Haug, Alisha; Richter, Sven; Alenezi, Haithanm; Herold-Mende, Christel; Lamszus, Katrin; Synowitz, Michael; Schick, Joel; Kälin, Roland; Glass, Rainer
• Is Part Of: Neuro-oncology. Volume 21(2019)Supplement 6
• Page Start: vi70
• Page End: vi71
• Publication Date: 2019-11-11
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noz175.286
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Glioblastoma (GBM) therapy could strongly profit from simplified procedures for personalized medicine. Cannabidiol (CBD) is explored for GBM-patients, but the mode of drug-action is largely unknown and stratification markers are missing. We investigated CBD-induced cytotoxicity in a panel of human primary GBM cells as well as transgenic mouse gliomas and in different orthotopic or transgenic in vivo models. We observed therapeutic efficiency of CBD in a subset of GBM, obtained genetic markers indicating CBD-sensitive GBM and found that the p53 status segregated cell-death modes. Genome wide loss of function screening, transcription factor binding studies and knockout-models indicated a central for role for NFkB (RelA) in CBD-initiated GBM-death. CBD mediated nuclear import of RelA lacking an essential post-translational modification and reduced RelA-activity. CBD altered redox levels specifically in drug-sensitive GBM and ROS-levels in unstimulated GBM predicted therapeutic response. Hence, quantifying ROS in GBM represents a simple bioassay to identify individuals potentially profiting from CBD-application in neurooncology.