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Title

Coordinate β-adrenergic inhibition of mitochondrial activity and angiogenesis arrest tumor growth

AuthorsNuevo-Tapioles, Cristina CSIC ORCID; Santacatterina, Fulvio CSIC ORCID; Stamatakis, Konstantinos CSIC ORCID; Núñez de Arenas, Cristina; Gómez de Cedrón, Marta; Formentini, Laura CSIC ORCID; Cuezva, José M
Issue Date2020
PublisherNature Publishing Group
CitationNature Communications 11 (2020)
AbstractMitochondrial metabolism has emerged as a promising target against the mechanisms of tumor growth. Herein, we have screened an FDA-approved library to identify drugs that inhibit mitochondrial respiration. The β1-blocker nebivolol specifically hinders oxidative phosphorylation in cancer cells by concertedly inhibiting Complex I and ATP synthase activities. Complex I inhibition is mediated by interfering the phosphorylation of NDUFS7. Inhibition of the ATP synthase is exerted by the overexpression and binding of the ATPase Inhibitory Factor 1 (IF1) to the enzyme. Remarkably, nebivolol also arrests tumor angiogenesis by arresting endothelial cell proliferation. Altogether, targeting mitochondria and angiogenesis triggers a metabolic and oxidative stress crisis that restricts the growth of colon and breast carcinomas. Nebivolol holds great promise to be repurposed for the treatment of cancer patients.
Publisher version (URL)http://dx.doi.org/10.1038/s41467-020-17384-1
URIhttp://hdl.handle.net/10261/235671
Identifiersdoi: 10.1038/s41467-020-17384-1
issn: 2041-1723
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