DELTA(9)-TETRAHYDROCANNABINOL INDUCES APOPTOSIS IN C6 GLIOMA-CELLS

Delta(9)-Tetrahydrocannabinol (THC), the major active component of mar ijuana, induced apoptosis in C6.9 glioma cells, as determined by DNA f ragmentation and loss of plasma membrane asymmetry. THC stimulated sph ingomyelin hydrolysis in C6.9 glioma cells. THC and N-acetglsphingosin e, a cell-permeable ceramide analog, induced apoptosis in several tran sformed neural cells but not in primary astrocytes or neurons. Althoug h glioma C6.9 cells expressed the CB1 cannabinoid receptor, neither TH C-induced apoptosis nor THC-induced sphingomyelin breakdown mere preve nted by SR141716, a specific antagonist of that receptor. Results thus show that THC-induced apoptosis in glioma C6.9 cells may rely on a CB 1 receptor-independent stimulation of sphingomyelin breakdown. (C) 199 8 Federation of European Biochemical Societies.