title: The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells.
abstract: Recently, we have shown that the non-psychoactive cannabinoid compound cannabidiol (CBD) induces apoptosis of glioma cells in vitro and tumor regression in vivo. The present study investigated a possible involvement of caspase activation and reactive oxygen species (ROS) induction in the apoptotic effect of CBD. CBD produced a gradual, time-dependent activation of caspase-3, which preceded the appearance of apoptotic death. In addiction, release of cytochrome c and caspase-9 and caspase-8 activation were detected. The exposure to CBD caused in glioma cells an early production of ROS, depletion of intracellular glutathione and increase activity of glutathione reductase and glutathione peroxidase enzymes. Under the same experimental condition, CBD did not impair primary glia. Thus, we found a different sensitivity to the anti-proliferative effect of CBD in human glioma cells and non-transformed cells that appears closely related to a selective ability of CBD in inducing ROS production and caspase activation in tumor cells.
authors.affiliation: Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, via Vanvitelli 32, 20129 Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Massi
authors.forename: A
authors.initials: A
authors.lastname: Vaccani
authors.forename: S
authors.initials: S
authors.lastname: Bianchessi
authors.forename: B
authors.initials: B
authors.lastname: Costa
authors.forename: P
authors.initials: P
authors.lastname: Macchi
authors.forename: D
authors.initials: D
authors.lastname: Parolaro
mesh_terms: D002185:Cannabidiol / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004789:Enzyme Activation; D005910:Glioma / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D002185:Cannabidiol; D020169:Caspases; D005978:Glutathione