Oxidative stress induced by the anti-cancer agents, plumbagin, and atovaquone, inhibits ion transport through Na⁺/K⁺-ATPase.

ABSTRACT: Oxidative stress inhibits Na⁺/K⁺-ATPase (NKA), the ion channel that maintains membrane potential. Here, we investigate the role of oxidative stress-mediated by plumbagin and atovaquone in the inhibition of NKA activity. We confirm that plumbagin and atovaquone inhibit the proliferation of three human (OVCAR-3, SKOV-3, and TYKNu) and one mouse (ID8) ovarian cancer cell lines. The oxygen radical scavenger, N-acetylcysteine (NAC), attenuates the chemotoxicity of plumbagin and atovaquone. Whole-cell patch clamping demonstrates that plumbagin and atovaquone inhibit outward and the inward current flowing through NKA in SKOV-3 and OVCAR-3. Although both drugs decrease cellular ATP; providing exogenous ATP (5 mM) in the pipet solution used during patch clamping did not recove

SUBMITTER: Alharbi Y 

PROVIDER: S-EPMC7659016 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature