Redox-Crippled MitoQ Potently Inhibits Breast Cancer and Glioma Cell Proliferation
Mitochondria-targeted coenzyme Q10 (Mito-ubiquinone, Mito-quinone mesylate, or MitoQ) has been shown to be an effective antimetastatic drug in patients with triple-negative breast cancer. MitoQ, sold as a nutritional supplement, prevents breast cancer recurrence. The proposed mechanism of action involves the inhibition of reactive oxygen species by MitoQ via a redox-cycling mechanism between the oxidized form, MitoQ, and the fully reduced form, mitochondria-targeted ubiquinol.
To fully corroborate this antioxidant mechanism, the authors – Balaraman Kalyanaraman, PhD, professor of biophysics and the Harry R. & Angeline E. Quadracci Professor in Parkinson’s Research at MCW; Gang Cheng, PhD, assistant professor of biophysics at MCW; and Hakim Karoui, PhD and Micael Hardy, PhD, of Aix-Marseille Université, France – substituted the hydroquinone group (-OH) with the methoxy group (-OCH3). Unlike MitoQ, the redox-crippled derivative—dimethoxy MitoQ (DM-MitoQ)—lacks redox-cycling between the quinone and hydroquinone forms. DM-MitoQ was not converted to MitoQ in human breast cancer cells. The authors tested the antiproliferative effects of both MitoQ and DM-MitoQ in triple-negative human breast cancer, brain-homing cancer, and glioma cells, and found that DM-MitoQ inhibited proliferation of these cells slightly more potently than MitoQ.
In their article, titled “Redox-crippled MitoQ potently inhibits breast cancer and glioma cell proliferation: A negative control for verifying the antioxidant mechanism of MitoQ in cancer and other oxidative pathologies,” and published in Free Radical Biology and Medicine, the authors conclude that inhibition of mitochondrial oxidative phosphorylation by MitoQ is responsible for inhibition of breast cancer and glioma proliferation and metastasis. Blunting the antioxidant effect using the redox-crippled DM-MitoQ can serve as a useful negative control in corroborating the involvement of free radical-mediated processes (e.g., ferroptosis, protein oxidation/nitration) using MitoQ in other oxidative pathologies.