title: The effects of cannabidiol and its synergism with bortezomib in multiple myeloma cell lines. A role for transient receptor potential vanilloid type-2.
abstract: 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.
authors.affiliation: Section of Experimental Medicine, School of Pharmacy, University of Camerino, Camerino, Italy.
authors.forename: Maria Beatrice
authors.initials: MB
authors.lastname: Morelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Offidani
authors.forename: Francesco
authors.initials: F
authors.lastname: Alesiani
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Discepoli
authors.forename: Sonia
authors.initials: S
authors.lastname: Liberati
authors.forename: Attilio
authors.initials: A
authors.lastname: Olivieri
authors.forename: Matteo
authors.initials: M
authors.lastname: Santoni
authors.forename: Giorgio
authors.initials: G
authors.lastname: Santoni
authors.forename: Pietro
authors.initials: P
authors.lastname: Leoni
authors.forename: Massimo
authors.initials: M
authors.lastname: Nabissi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D002185:Cannabidiol / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050916:TRPV Cation Channels / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D016328:NF-kappa B; D011719:Pyrazines; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C400769:TRPV2 protein, human; D002185:Cannabidiol; D000069286:Bortezomib
keywords: bortezomib; cannabidiol; multiple myeloma; transient receptor potential vanilloid type 2