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Updated: Sep 23, 2025

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Atovaquone: An Inhibitor of Oxidative Phosphorylation as Studied in Gynecologic Cancers

Arvinder Kapur1, Pooja Mehta2, Aaron D Simmons3

  • 1Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, WI 53705, USA.

Cancers
|May 14, 2022
PubMed

Insights

Atovaquone, an anti-malarial drug, inhibits cancer cell proliferation and ovarian cancer growth by blocking oxidative phosphorylation. This study provides preclinical data supporting its potential as a gynecologic cancer therapeutic.

Area of Science:

  • Oncology
  • Biochemistry
  • Pharmacology

Background:

  • Oxidative phosphorylation is a key metabolic pathway in cancer.
  • Atovaquone is an FDA-approved anti-malarial drug that inhibits oxidative phosphorylation.

Purpose of the Study:

  • To investigate the anti-cancer properties of atovaquone.
  • To evaluate atovaquone's efficacy in ovarian cancer models.
  • To understand the mechanism of atovaquone's anti-cancer effects.

Main Methods:

  • Cell proliferation assays in 2D culture.
  • In vivo studies using mouse models with ovarian cancer.
  • Treatment of patient-derived cancer stem-like cells and spheroids.
  • Flow and imaging cytometry to assess oxygen radicals.
  • Seahorse XFe96 analysis for oxygen consumption rate (OCR).
  • NMR metabolomics to analyze metabolic shifts.

Main Results:

  • Atovaquone inhibited cancer cell proliferation and ovarian cancer growth in vitro and in vivo.
  • Atovaquone decreased oxygen consumption and ATP production.
  • Oxygen radical flux was primarily localized in mitochondria.
  • Atovaquone reduced the viability of cancer stem-like cells and spheroids.
  • Metabolomic analysis revealed significant shifts in cellular metabolism.

Conclusions:

  • Atovaquone demonstrates potent anti-cancer activity against ovarian cancer.
  • The drug's mechanism involves inhibition of oxidative phosphorylation and mitochondrial function.
  • Preclinical data support further investigation of atovaquone as a gynecologic cancer therapeutic.
Keywords:
metabolismmitochondriaoxidative phosphorylation

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