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

Area of Science:

• Oncology
• Mitochondrial Metabolism
• Drug Repurposing

Background:

• Mitochondrial metabolism is a key driver of tumor growth.
• Targeting cancer cell respiration offers a therapeutic strategy.
• Identifying existing drugs for repurposing can accelerate cancer treatment development.

Purpose of the Study:

• To screen FDA-approved drugs for inhibitors of mitochondrial respiration.
• To investigate the anti-cancer mechanisms of identified compounds.
• To evaluate the potential of nebivolol for cancer therapy.

Main Methods:

• Screening of an FDA-approved drug library.
• Assessing mitochondrial respiration and oxidative phosphorylation.
• Investigating the effects on Complex I and ATP synthase.
• Evaluating tumor angiogenesis and endothelial cell proliferation.

Main Results:

• Nebivolol inhibits mitochondrial Complex I and ATP synthase in cancer cells.
• Nebivolol interferes with NDUFS7 phosphorylation and increases IF1 binding to ATP synthase.
• Nebivolol arrests tumor angiogenesis by inhibiting endothelial cell proliferation.
• Nebivolol restricts the growth of colon and breast carcinomas.

Conclusions:

• Nebivolol effectively targets cancer cell mitochondria and angiogenesis.
• Repurposing nebivolol may offer a novel strategy for cancer treatment.
• Nebivolol induces metabolic and oxidative stress, restricting tumor growth.