The effects of cannabidiol and its synergism with bortezomib in multiple myeloma cell lines. A role for transient receptor potential vanilloid type-2

Maria Beatrice Morelli, Massimo Offidani, Francesco Alesiani, Giancarlo Discepoli, Sonia Liberati, Attilio Olivieri, Matteo Santoni, Giorgio Santoni, Pietro Leoni, Massimo Nabissi

Research output: Contribution to journalArticlepeer-review

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. What's new Cannabidiol, a non-psychoactive component of Cannabis, has antitumor properties. This study investigated whether cannabidiol could assist another drug, bortezomib, in fighting multiple myeloma. Although patients respond well to bortezomib at first, most develop resistance to it over time. The authors looked in myeloma cell lines and patient samples for a protein, TRPV2, which interacts with cannabidiol. They found that cannabidiol, working alone or in concert with bortezomib, kills multiple myeloma cells, particularly when TRPV2 was expressed. These data suggest that treatment with cannabidiol may help sidestep the problem of patients developing resistance to bortezomib.

Original languageEnglish
Pages (from-to)2534-2546
Number of pages13
JournalInternational Journal of Cancer
Volume134
Issue number11
DOIs
Publication statusPublished - Jun 1 2014

Keywords

  • bortezomib
  • cannabidiol
  • multiple myeloma
  • transient receptor potential vanilloid type 2

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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