Atovaquone exerts its anticancer effect by inhibiting Na+/K+-ATPase ion transport in canine cancer cells

Background and Aim: New anticancer drugs are being developed to avoid the toxicity chemoresistance of currently available drugs. The Food Drug Administration-approved anti-malarial drug atovaquone is known act as a selective oxidative phosphorylation inhibitor in mitochondria by competing with CO Q10 (mitochondrial complex II III). This study aimed investigate effect examining Na+/K+-ATPase (NKA) activity various canine cell lines. Materials Methods: Canine lines were treated concentrations (2.5, 5, 10, 15, 20 µM) for 24, 48, 72 h. Human used control validate cancer activities against measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl- 2H-tetrazolium bromideassay. metabolic was determined measuring nicotinamide adenine dinucleotide phosphate-dependent cellular oxidoreductase enzymes. NKA single-cell patch clamping assay. Results: Atovaquone-induced apoptosis elevating concentration reactive oxygen species (ROS) tumor cells, leading death. Treatment cells N-acetylcysteine (ROS inhibitor) reduced drug. Furthermore, inhibited more than 45% ion current. Conclusion: demonstrated effects data may prove beneficial repurposing new agent clinical trials, which might aid fighting human cancer. Keywords: atovaquone, electrophysiology, Na+/K+-ATPase, phosphorylation, stress, plumbagin.