Vet World   Vol.16   June-2023  Article-1

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 and chemoresistance of the currently available drugs. The Food and Drug Administration-approved anti-malarial drug atovaquone is known to act as a selective oxidative phosphorylation inhibitor in the mitochondria by competing with CO Q10 (mitochondrial complex II and III). This study aimed to investigate the effect of atovaquone by examining the Na+/K+-ATPase (NKA) activity in various canine cell lines.

Materials and Methods: Canine cell lines were treated with various concentrations (2.5, 5, 10, 15, and 20 µM) of atovaquone for 24, 48, and 72 h. Human cell lines were used as a control to validate the canine cancer cell lines. The activities of the drugs against the cancer cell lines were measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl- 2H-tetrazolium bromideassay. The cell metabolic activity was determined by measuring the activities of the nicotinamide adenine dinucleotide phosphate-dependent cellular oxidoreductase enzymes. The NKA activity was measured using the single-cell patch clamping assay.

Results: Atovaquone-induced apoptosis by elevating the concentration of reactive oxygen species (ROS) in the tumor cells, leading to cell death. Treatment of canine cancer cells with N-acetylcysteine (ROS inhibitor) reduced the activity of the drug. Furthermore, atovaquone inhibited more than 45% of the NKA ion current.

Conclusion: This study demonstrated effects of atovaquone against canine cancer cell lines. The data may prove beneficial in repurposing the drug as a new anticancer agent in canine clinical trials, which might aid in fighting human cancer. Keywords: atovaquone, electrophysiology, Na+/K+-ATPase, oxidative phosphorylation, oxidative stress, plumbagin.

Keywords: atovaquone, electrophysiology, Na+/K+-ATPase, oxidative phosphorylation, oxidative stress, plumbagin.

How to cite this article: Alharbi Y (2023) Atovaquone exerts its anticancer effect by inhibiting Na

Received: 14-11-2022  Accepted: 29-03-2023     Published online: 04-06-2023

Corresponding author: Yousef Alharbi   E-mail: yhrby@qu.edu.sa

DOI: 10.14202/vetworld.2023.1185-1192

Copyright: Alharbi, et al. This article is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.