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MCW Researchers Publish Study on Potent Inhibition of Tumor Cell Proliferation and Immunoregulatory Function by Mitochondria-targeted Atovaquone

Antimalaria drug atovaquone (ATO) has been found to exert a profound antiproliferative effect in several cancer cells (including breast, ovarian, and glioma), inhibiting mitochondrial complex III and cell respiration. To enhance the chemotherapeutic efficacy and oxidative phosphorylation inhibition, MCW researchers developed a mitochondria-targeted triphenylphosphonium-conjugated ATO with varying alkyl side chains.

As detailed in their article, “Potent inhibition of tumor cell proliferation and immunoregulatory function by mitochondria-targeted atovaquone” published in Scientific Reports, study results show that triphenylphosphonium-conjugated ATO potently enhanced the antiproliferative effect of ATO in cancer cells and, depending upon the alkyl chain length, the molecular target of inhibition changes from mitochondrial complex III to complex I. Mitochondrial target shifting may have immunoregulatory implications.

The corresponding author of the article is Balaraman Kalyanaraman, PhD, chair and professor of biophysics and the Harry R. & Angeline E. Quadracci Professor in Parkinson’s Research. Other collaborating authors include Gang Cheng, PhD, research scientist II in biophysics; Micael Hardy, PhD, Aix-Marseille Université, France; Paytsar Topchyan, MS, MSTP graduate student in microbiology & immunology; Ryan Zander, PhD, postdoctoral fellow at Versiti Blood Research Institute; Peter Volberding, PhD, postdoctoral fellow at Versiti Blood Research Institute; Weiguo Cui, MD, PhD, assistant professor of microbiology & immunology, and investigator at Versiti Blood Research Institute.

The full article can be viewed on the Scientific Reports website.