MitoQ Inhibits Human Breast Cancer Cell Migration, Invasion and Clonogenicity

• Published in: Cancers Vol. 14; no. 6; p. 1516
• Main Authors: Capeloa, Tania, Krzystyniak, Joanna, d'Hose, Donatienne, Canas Rodriguez, Amanda, Payen, Valery L, Zampieri, Luca X, Van de Velde, Justine A, Benyahia, Zohra, Pranzini, Erica, Vazeille, Thibaut, Fransolet, Maude, Bouzin, Caroline, Brusa, Davide, Michiels, Carine, Gallez, Bernard, Murphy, Michael P, Porporato, Paolo E, Sonveaux, Pierre
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.03.2022; MDPI
• Subjects: Antioxidants; Breast cancer; Cell adhesion & migration; Cell culture; Cell cycle; Cell migration; Clinical trials; clonogenicity; Drug dosages; ErbB-2 protein; Focal adhesion kinase; Growth factors; Hypoxia; Intracellular signalling; invasion; Invasiveness; Mesenchyme; Metabolism; Metastases; Metastasis; Microenvironments; migration; Mitochondria; Phenotypes; Progenitor cells; Solid tumors; spheroids; Stem cells; Superoxide; Transforming growth factor-b; Tumor cell lines; Tumors; Belgium; Germany; clonogenicity; mitochondrial superoxide; MitoQ; invasion; metastasis; mitochondria; migration; breast cancer; spheroids; mitochondria-targeted antioxidant
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14061516

To successfully generate distant metastases, metastatic progenitor cells must simultaneously possess mesenchymal characteristics, resist to anoïkis, migrate and invade directionally, resist to redox and shear stresses in the systemic circulation, and possess stem cell characteristics. These cells primarily originate from metabolically hostile areas of the primary tumor, where oxygen and nutrient deprivation, together with metabolic waste accumulation, exert a strong selection pressure promoting evasion. Here, we followed the hypothesis according to which metastasis as a whole implies the existence of metabolic sensors. Among others, mitochondria are singled out as a major source of superoxide that supports the metastatic phenotype. Molecularly, stressed cancer cells increase mitochondrial superoxide production, which activates the transforming growth factor-β pathway through src directly within mitochondria, ultimately activating focal adhesion kinase Pyk2. The existence of mitochondria-targeted antioxidants constitutes an opportunity to interfere with the metastatic process. Here, using aggressive triple-negative and HER2-positive human breast cancer cell lines as models, we report that MitoQ inhibits all the metastatic traits that we tested in vitro. Compared to other mitochondria-targeted antioxidants, MitoQ already successfully passed Phase I safety clinical trials, which provides an important incentive for future preclinical and clinical evaluations of this drug for the prevention of breast cancer metastasis.