Cannabidiol directly targets mitochondria and disturbs calcium homeostasis in acute lymphoblastic leukemia

Anticancer properties of non-psychoactive cannabinoid cannabidiol (CBD) have been demonstrated on tumors of different histogenesis. Different molecular targets for CBD were proposed, including cannabinoid receptors and some plasma membrane ion channels. Here we have shown that cell lines derived from acute lymphoblastic leukemia of T lineage (T-ALL), but not resting healthy T cells, are highly sensitive to CBD treatment. CBD effect does not depend on cannabinoid receptors or plasma membrane Ca²⁺-permeable channels. Instead, CBD directly targets mitochondria and alters their capacity to handle Ca²⁺. At lethal concentrations, CBD causes mitochondrial Ca²⁺ overload, stable mitochondrial transition pore formation and cell death. Our results suggest that CBD is an attractive candidate to be included into chemotherapeutic protocols for T-ALL treatment.