“Cell fate events are regulated by different endogenous developmental factors such as cell microenvironment, external or remote signals and epigenetic regulation. Among the many regulatory factors, endocannabinoid associated signalling pathways are known to lead several of these events in the developing nervous system and in the adult brain. Interestingly, endocannabinoids exert its modulatory actions in health and pathological conditions. Endocannabinoid signalling can promote cell survival acting on non-transformed brain cells (neurons, astrocytes or oligodendrocytes) while can either have a protumoural or antitumoural effect on transformed cells. Moreover, endocannabinoids are able to attenuate detrimental effects on neurogenesis and neuroinflammation associated with ageing. Thus, the endocannabinoid system emerges as an important regulator of cell fate to control cell survival/cell death decisions depending on the cell type and its environment.”
“Multiple myeloma (MM) is a plasma cell (PC) malignancy characterised by the accumulation of a monoclonal PC population in the bone marrow (BM).
Cannabidiol (CBD) is a non-psychoactive cannabinoid with antitumoural activities, and the transient receptor potential vanilloid type-2 (TRPV2) channel has been reported as a potential CBD receptor.
TRPV2 activation by CBD decreases proliferation and increases susceptibility to drug-induced cell death in human cancer cells.
However, no functional role has been ascribed to CBD and TRPV2 in MM. In this study, we identified the presence of heterogeneous CD138+TRPV2+ and CD138+TRPV2- PC populations in MM patients, whereas only the CD138+ TRPV2- population was present in RPMI8226 and U266 MM cell lines.
Because bortezomib (BORT) is commonly used in MM treatment, we investigated the effects of CBD and BORT in CD138+TRPV2- MM cells and in MM cell lines transfected with TRPV2 (CD138+TRPV2+).
These results showed that CBD by itself or in synergy with BORT strongly inhibited growth, arrested cell cycle progression and induced MM cells death by regulating the ERK, AKT and NF-κB pathways with major effects in TRPV2+ cells.
These data provide a rationale for using CBD to increase the activity of proteasome inhibitors in MM.”