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

Cristina Nuevo-Tapioles, Fulvio Santacatterina, Konstantinos Stamatakis, Cristina Núñez de Arenas, Marta Gómez de Cedrón, Laura Formentini and José M. Cuezva ()
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Cristina Nuevo-Tapioles: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM)
Fulvio Santacatterina: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM)
Konstantinos Stamatakis: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM)
Cristina Núñez de Arenas: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM)
Marta Gómez de Cedrón: Universidad Autónoma de Madrid
Laura Formentini: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM)
José M. Cuezva: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM)

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: Abstract Mitochondrial 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17384-1

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DOI: 10.1038/s41467-020-17384-1

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