Cannabidiol protects C2C12 myotubes against cisplatin-induced atrophy by regulating oxidative stress

Cancer and chemotherapy can both cause cachexia, a complex multi-organ syndrome characterized by body weight loss, due to adipose tissue and skeletal muscle wasting. Changes in body weight and muscle mass are predictive of response to chemotherapy, incidence of treatment-related complications and, ultimately, patient survival, but there are currently still no clear therapeutic strategies to counteract cachexia. Cannabidiol (CBD) is a bioactive phytocannabinoid produced from a plant named Cannabis sativa. In recent years, CBD has demonstrated beneficial effects on maintaining skeletal muscle mass, function and metabolism in models of muscular dystrophy or diet-induced obesity. Here, we used a model of myotubes in culture to evaluate the potential beneficial effects of CBD on cisplatin-induced skeletal muscle wasting. 24-h cisplatin treatment resulted in a ≈30% reduction in myotube diameter, driven by a drastic reduction in protein synthesis rate and a twofold increase in proteolysis. 24-h cisplatin treatment also significantly increased myotube TBARS content, catalase activity and antioxidant system mRNA levels (GPX1, SOD1, SOD2 and CAT) indicating increased oxidative stress. 24-h cisplatin treatment also increased the mitochondrial protein content of NDUFB8, UQCRC2, COX4 and VDAC1, which are involved in mitochondrial respiration and control of apoptosis. Importantly, CBD was found to antagonize chemotherapy-induced C2C12 myotube atrophy by promoting protein homeostasis and reducing oxidative stress. Our results show that CBD could be used as an adjuvant in the treatment of cancer cachexia to help maintain muscle mass and improve patient quality of life.