Meccanismi cellulari implicati nell'effetto antitumorale del cannabidiolo su cellule di glioma umano U87-MG e caratterizzazione delle sue proprietà antiangiogeniche.

In this study we evaluated the ability of the non-psychoactive cannabinoid compound cannabidiol (CBD) to limit glioma cells invasiveness and to interfere with the most relevant intracellular pathways involved in tumor development, together with its ability to modulate angiogenic process. We found that CBD inhibited U87-MG cells invasiveness, caused a down-regulation of ERK and Akt activation, reduced HIF-1α expression and decreased the level of several proteins specifically involved in growth, invasion and angiogenesis. CBD also induced endothelial cell cytostasis, without inducing apoptosis, inhibited their migration, invasion and sprouting in vitro, and angiogenesis in vivo, with correspondent down-modulation of several angiogenesis-related molecules. These results provide new insight into CBD antitumor action, showing multiple tumoral features and molecular pathways affected by CBD. Moreover, its dual effect on both glioma and endothelial cells reinforces the hypothesis of its possible use as effective anticancer agent. Finally we evaluated the antitumor effects of other non-psychoactive cannabinoid compounds, not thoroughly investigate so far. These compounds inhibited, with different extents, glioma cell viability, migration and invasiveness, through mechanisms nor cannabinoid or vanilloid receptors-mediated. Our results contribute to clarify the pharmacology of these molecules, although further studies are needed to understand cellular mechanisms involved in their effects.