Aspirin Induces Mitochondrial Ca2+ Remodeling in Tumor Cells via ROS‒Depolarization‒Voltage-Gated Ca2+ Entry.

ABSTRACT: Aspirin (acetylsalicylic acid) and its metabolite salicylate, have an anti-melanoma effect by evoking mitochondrial dysfunction through poorly understood mechanisms. Depolarization of the plasma membrane potential leads to voltage-gated Ca2+ entry (VGCE) and caspase-3 activation. In the present study, we investigated the role of depolarization and VGCE in aspirin's anti-melanoma effect. Aspirin and to a lesser extent, salicylate (≥2.5 mM) induced a rapid (within seconds) depolarization, while they caused comparable levels of depolarization with a lag of 2~4 h. Reactive oxygen species (ROS) generation also occurred in the two-time points, and antioxidants abolished the early ROS generation and depolarization. At the same concentrations, the two drugs induced apoptotic and necrotic cell deat

SUBMITTER: Fujikawa I 

PROVIDER: S-EPMC7370041 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature