Adenosine triphosphate induced cell death: Mechanisms and implications in cancer biology and therapy

Figure 3 Illustration of the mechanism of adenosine triphosphate induced cell death, which involves several interconnected pathways. Upon binding to the purinergic receptor P2X7 (P2X7R), extracellular adenosine triphosphate (ATP) induces a surge in intracellular calcium levels, leading to caspase activation and subsequent cell death. Additionally, ATP activates the NOD-like receptor family pyrin domain containing 3 inflammasome by releasing High Mobility Group Box 1/Toll-Like Receptor 4, triggering caspase-1 activation and promoting cell apoptosis. The interaction between ATP and P2X7Rs also activates the Nuclear Factor-kappa B and Phosphatidylinositol 3-kinase-protein kinase B/hypoxia-inducible factor pathways, resulting in DNA damage and cell death. Simultaneously, the continuous accumulation of intracellular Ca²⁺ stimulates the opening of the mitochondrial permeability transition pore, leading to DNA damage and ultimately cell necrosis. Ca²⁺ induces mitochondria to release cytochrome c, further contributing to the apoptotic process. Moreover, ATP-triggered cellular demise instigates a transformative shift within the extracellular microenvironment, concurrently unleashing a plethora of cytokines. Lastly, apart from elucidating the fundamental underpinnings of ATP induced cell death, this Figure also encapsulates a synthesized appraisal of the plausible mechanisms governing microenvironmental equilibrium, as extrapolated from relevant literature. ATP: Adenosine triphosphate; NF-κB: Nuclear Factor-kappa B; NLRP3: NOD-like receptor family pyrin domain containing 3; PI3K-AKT: Phosphatidylinositol 3-kinase-protein kinase B; ROS: Reactive oxygen species; TNF-α: Tumor necrosis factor-alpha; IL: Interleukin; ASC: Apoptosis-related speckle-like protein; STAT: Signal transducer and activator of transcription.