The effects of cannabidiol and its synergism with bortezomib in multiple myeloma cell lines. A role for transient receptor potential vanilloid type‐2. Issue 11 (2nd December 2013)

• Record Type: Journal Article
• Authors: Morelli, Maria Beatrice; Offidani, Massimo; Alesiani, Francesco; Discepoli, Giancarlo; Liberati, Sonia; Olivieri, Attilio; Santoni, Matteo; Santoni, Giorgio; Leoni, Pietro; Nabissi, Massimo
• Is Part Of: International journal of cancer. Volume 134:Issue 11(2014:Jun. 01)
• Page Start: 2534
• Page End: 2546
• Publication Date: 2013-12-02
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28591
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>TRPV2</italic> (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.</p> </abstract>