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

Nature Communications
Cristina Nuevo-TapiolesJosé M Cuezva

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.

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Citations

Oct 30, 2020·International Journal of Molecular Sciences·Boris MravecLuba Hunakova
Mar 5, 2021·Molecular Biology Reports·Zongyu LiuKai Zhang
Apr 14, 2021·Future Medicinal Chemistry·William A Denny
Jul 19, 2021·Human Molecular Genetics·Cristina Nuevo-TapiolesJosé M Cuezva

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Methods Mentioned

BETA
immunoprecipitation
xenograft
electrophoresis
flow cytometry
Flow
Assay
protein assay
confocal microscopy
PCR
reverse phase chromatography

Software Mentioned

PEAKS Studio
ImageJ
GraphPad Prism
SPSS
Excel

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