Mitoquinone (MitoQ) is a synthetically-modified, redox-active ubiquinone compound that accumulates predominantly in mitochondria. We evaluated the potential use of MitoQ as an anti-cancer agent and found that it is 30-fold more cytotoxic to breast cancer cells than to healthy mammary cells. MitoQ caused irreversible inhibition of the clonogenic growth of breast cancer cells by a combination of autophagic and apoptotic cell death mechanisms, with autophagy playing the major role. None of the cytotoxic effects of MitoQ were seen with the parent ubiquinone coenzyme Q10. Growth inhibition from MitoQ was associated with G1/S cell cycle arrest and phosphorylation of the checkpoint kinases Chk1 and Chk2. A possible role for oxidative stress in MitoQ activity is supported by observed increases in products of hydroethidine oxidation (2-hydroxyethidium, ethidium and diethidium) at cytotoxic concentrations of MitoQ. We will present data showing that Nrf2 and Keap1 regulate the response to the oxidative perturbations caused by MitoQ.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4452.