Oxidative phosphorylation is an active metabolic pathway in
cancer.
Atovaquone is an oral medication that inhibits oxidative phosphorylation and is FDA-approved for the treatment of
malaria. We investigated its potential anti-
cancer properties by measuring cell proliferation in 2D culture. The clinical formulation of
atovaquone,
Mepron, was given to mice with
ovarian cancers to monitor its effects on
tumor and
ascites. Patient-derived
cancer stem-like cells and spheroids implanted in NSG mice were treated with
atovaquone.
Atovaquone inhibited the proliferation of
cancer cells and
ovarian cancer growth in vitro and in vivo. The effect of
atovaquone on
oxygen radicals was determined using flow and imaging cytometry. The oxygen consumption rate (OCR) in adherent cells was measured using a Seahorse XFe96 Extracellular Flux Analyzer. Oxygen consumption and
ATP production were inhibited by
atovaquone. Imaging cytometry indicated that the majority of the
oxygen radical flux triggered by
atovaquone occurred in the mitochondria.
Atovaquone decreased the viability of patient-derived
cancer stem-like cells and spheroids implanted in NSG mice. NMR metabolomics showed shifts in glycolysis, citric acid cycle, electron transport chain, phosphotransfer, and metabolism following
atovaquone treatment. Our studies provide the mechanistic understanding and preclinical data to support the further investigation of
atovaquone's potential as a gynecologic
cancer therapeutic.