Potent inhibition of tumour cell proliferation and immunoregulatory function by mitochondria-targeted atovaquone.

ABSTRACT: The FDA-approved prophylactic antimalarial drug atovaquone (ATO) recently was repurposed as an antitumor drug. Studies show that ATO exerts a profound antiproliferative effect in several cancer cells, including breast, ovarian, and glioma. Analogous to the mechanism of action proposed in parasites, ATO inhibits mitochondrial complex III and cell respiration. To enhance the chemotherapeutic efficacy and oxidative phosphorylation inhibition, we developed a mitochondria-targeted triphenylphosphonium-conjugated ATO with varying alkyl side chains (Mito₄-ATO, Mito₁₀-ATO, Mito₁₂-ATO, and Mito₁₆-ATO). Results show, for the first time, that triphenylphosphonium-conjugated ATO potently enhanced the antiproliferative effect of ATO in cancer cells and, depen

SUBMITTER: Cheng G 

PROVIDER: S-EPMC7578061 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature