Medicinal cannabis is attracting increasing attention for its therapeutic potential in cancer treatment due to its ability to modulate key signaling pathways associated with tumor progression and cell death. Among various mechanisms, cannabinoids have recently been shown to trigger ferroptosis that is a regulated, iron-dependent form of cell death characterized by lipid peroxidation and glutathione depletion. This review focuses on the emerging role of cannabinoids in inducing ferroptosis in cancer cells. Cannabinoids, particularly non-psychoactive compounds such as cannabidiol (CBD), have been shown to disrupt redox homeostasis by suppressing the cystine/glutamate antiporter system Xc-, depleting intracellular glutathione, and inhibiting glutathione peroxidase 4 (GPX4) activity. These events lead to excessive lipid peroxidation and ultimately cause ferroptotic cell death. Furthermore, cannabinoids disrupt iron metabolism, promote ferritinophagy, and affect certain transcriptional regulators, making tumor cells more susceptible to ferroptosis. Cannabinoid-induced ferroptosis has been observed to be particularly selective in cancer cells, providing a strategic advantage in targeting treatment-resistant tumors. Despite encouraging preclinical evidence, studies directly linking cannabinoids to ferroptosis are still limited, and clinical data are lacking. Future research should focus on improving formulation strategies, identifying reliable ferroptosis biomarkers, and validating the clinical significance of these pathways in cannabinoid-based anticancer therapies.
Filiz Ateş (Mon,) studied this question.