Fig. 8: Proposed mechanism for the CBD effect on T-ALL cells. | Cell Death & Disease

Fig. 8: Proposed mechanism for the CBD effect on T-ALL cells.

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

Fig. 8

Highly lipophilic CBD readily permeates plasma membrane and enters the cytosol, approaching mitochondria. Direct CBD interaction with VDAC favors the channel closed substate with increased Ca2+ permeability. It favors mitochondrial Ca2+ uptake through VDAC and MCU, leading to the mitochondrial Ca2+ overload that promotes the mPTP formation, Δψm loss, mitochondrial swelling, and cristae disruption. mPTP opening promotes the Cyt-C release from mitochondria. In cytoplasm, Cyt-C may orchestrate the apoptosome formation, caspases´ activation, and triggers the intrinsic apoptosis. mPTP rapidly triggers Ca2+ release from the ER, which tends to promote the mitochondrial Ca2+ overload in a feedforward manner. The CBD-induced dysfunction of mitochondria is accompanied by severe oxidative stress and rapid loss of ATP production, resulting in the MPT-driven necrosis. Autophagy occurs in T-ALL cells treated with sublethal CBD concentrations

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