Anticancer effect of Minor Phytocannabinoids in Preclinical Models of Multiple Myeloma

Multiple myeloma (MM) is a blood cancer caused by uncontrolled growth of clonal plasmacells. Bone disease is responsible for the severe complications of MM and is caused by myeloma cells infiltrating the bone marrow and inducing osteoclast activation. To date, no treatment for MM is truly curative, since patients relapse and become refractory to all drug classes. Cannabinoids are already used as palliative in cancer patients. Furthermore, their proper anticancer effect was demonstrated in many cancer models in vitro, in vivo and in clinical trials. Anyway, only little is known about the effect of cannabinoids on MM and no data has been provided on minor phytocannabinoids such as cannabigerol (CBG), cannabichromene (CBC), cannabinol (CBN) and cannabidivarin (CBDV). Scientific literature reported also cannabinoids beneficial effect against bone disease. Here, we investigated the cytotoxic effect of CBG, CBC, CBN and CBDV in vitro in MM cell lines, obtaining that the phytocannabinoids inhibited MM cell growth and induced necrotic cell death. Moreover, the phytocannabinoids reduced the invasion of MM cells toward osteoblast cells and the bone resorption in vitro. Subsequently, according to the in vitro results, we selected CBN for in vivo studies in a MM xenograft mice model. Results showed that CBN reduced tumor mass in vivo. Together, our results suggest that CBG, CBC, CBN and CBDV can be promising anticancer agents for MM.