CBD Disrupts Malme-3M Cell Metabolism via Glycolytic Shift and Redox Imbalance

Background: Accumulating evidence suggests that cannabidiol (CBD) exerts variable effects on cancer cells that influences cellular activity including growth. While anecdotal evidence abounds, mechanistic studies have lagged behind. Methods: CBD treatment on malignant fibroblast (Malme-3M) and benign BJ fibroblast cells was performed. LC MS/MS mass spectroscopy was used to measure metabolites from CBD treatment. Results: Data indicate a differential response between malignant fibroblast (Malme-3M) cells and benign fibroblasts (BJ) cells with respect to metabolites critical for primary metabolic function. A significant reduction in TCA metabolites is seen with a corresponding increase in glycolytic output in the Malme-3M cell line while a similar reduction in TCA activity in the fibroblasts appears to differentially activate fatty acid oxidation. ATP is significantly reduced in the Malme-3M cells with a corresponding decrease in metabolites associated with redox maintenance. Conclusions: This is the first metabolomics analyses of both normal and tumor derived cell lines after pre-treatment with CBD. The data suggest that the metabolic perturbation, because of CBD treatment, could reprogram and affect cellular metabolism and redox maintenance.