The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells

Recently, we have shown that the non-psychoactive cannabinoid compd. 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 prodn. of ROS, depletion of intracellular glutathione and increase activity of glutathione reductase and glutathione peroxidase enzymes. Under the same exptl. 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 prodn. and caspase activation in tumor cells.