An Examination of the Anti-Cancer Properties of Plant Cannabinoids in Preclinical Models of Mesothelioma

Abstract

Mesothelioma is an aggressive cancer with limited treatment options and a poor prognosis. Phytocannabinoids possess anti-tumour and palliative properties in multiple cancers, however their effects in mesothelioma are unknown. We investigated the anti-cancer effects and potential mechanisms of action for several phytocannabinoids in mesothelioma cell lines. A panel of 13 phytocannabinoids inhibited growth of human (MSTO and H2452) and rat (II-45) mesothelioma cells in vitro, and cannabidiol (CBD) and cannabigerol (CBG) were the most potent compounds. Treatment with CBD or CBG resulted in G0/G1 arrest, delayed entry into S phase and induced apoptosis. CBD and CBG also significantly reduced mesothelioma cell migration and invasion. These effects were supported by changes in the expression of genes associated with the cell cycle, proliferation, and cell movement following CBD or CBG treatment. Gene expression levels of CNR1, GPR55, and 5HT1A also increased with CBD or CBG treatment. However, treatment with CBD or CBG in a syngeneic orthotopic rat mesothelioma model was unable to increase survival. Our data show that cannabinoids have anti-cancer effects on mesothelioma cells in vitro and alternatives of drug delivery may be needed to enhance their effects in vivo.

The Impact Of Cannabinoids On Breast Cancer Cell Lines: A Meta-Analysis And Systematic Review Of Antitumoral Effects

“…Metastatic disease has a high mortality rate [49]. Cannabinoids have shown anti-invasion and antimigration effects.…”

“…Cannabinoids have shown anti-invasion and antimigration effects. Several research groups mainly conducted in vitro assays with glioblastoma, adenocarcinoma, HNSCC, and mesothelioma cells to test the effect of CBD at various concentrations [34,[49][50][51]. From the limited available studies, treatment of MDA-MB-23 with CBD caused a reduction in cell migration by inhibiting cAMP-dependent protein kinase A, ERK, and AKT signalling, and modulating the tumour microenvironment [28,32,52].…”

Cannabinoids in Medicine: A Multifaceted Exploration of Types, Therapeutic Applications, and Emerging Opportunities in Neurodegenerative Diseases and Cancer Therapy

“…Notably absent from this analysis was CNR2 as its expression was not observed across any mesothelioma cell lines. The treatments with both CBD and CBG led to the substantial upregulation of key genes associated with cannabinoid activity and the pathology of mesothelioma across the three mesothelioma cell lines examined [ 188 ]. Specifically, noteworthy upregulations were observed for cannabinoid CB1 receptor (CNR1), G-protein-coupled receptor 55 (GPR55), and 5-HT1a receptor (5HTR1A) when compared to vehicle-treated controls, with an approximately 50-fold increase in the expression of GPR55.…”

“…Interestingly, the CBD treatment had a variable impact on the mRNA expression of transient receptor potential vanilloid type 1 (TRPV1). While it influenced the expression of TRPV1 across most mesothelioma cell lines, an exception was noted in the case of H2452 cells [ 188 ]. The expression of TRPV2 or peroxisome proliferator-activated receptor gamma (PPARG) demonstrated cell-line-dependent variability.…”

Editorial: Cannabinoid interactions with ion channels, receptors, and the bio-membrane

“…Because each of these targets has an important role in many physiological processes and disease mechanisms, cannabinoids have therapeutic potential for disorders that originate throughout the body including, but perhaps not limited to, excitable tissues: muscles and nerves ( Devane et al, 1988 ; Elsohly, 2007 ; Ghovanloo and Ruben, 2021 ). Indeed, looking beyond CBD and THC, other “minor” plant cannabinoids have been more recently explored for their medicinal potential with preclinical research showing a diversity of potential therapeutic applications including anti-inflammatory, anti-cancer, anti-seizure, anxiolytic, and anti-emetic activities ( Anderson et al, 2019 ; 2021b ; 2021a ; Assareh et al, 2020 ; Rock et al, 2021 ; Colvin et al, 2022 ; Lowin et al, 2023 ). However, the modes of action of these cannabis constituents remain to be determined.…”