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07:39
SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs
Published on: June 28, 2019
Cardiac glycosides are broad-spectrum senolytics
Ana Guerrero1,2, Nicolás Herranz1,2, Bin Sun1,2
1MRC London Institute of Medical Sciences, London, UK.
Nature Metabolism
|December 5, 2019
Summary
Cardiac glycosides, like ouabain, act as senolytics, selectively killing senescent cells. This finding suggests potential new therapies for cancer and age-associated diseases.
Area of Science:
- Cellular biology
- Gerontology
- Pharmacology
Background:
- Cellular senescence is a state of irreversible cell cycle arrest.
- Senescence can be tumor suppressive but also promotes tumorigenesis via secreted factors.
- Senolytic drugs selectively eliminate senescent cells and show promise in age-related diseases.
Purpose of the Study:
- To investigate the senolytic potential of cardiac glycosides, specifically ouabain.
- To explore the mechanisms underlying ouabain-induced senescent cell death.
- To evaluate the efficacy of cardiac glycosides in combination with anti-cancer drugs and in models of aging and cancer.
Main Methods:
- Treatment of senescent cells with ouabain.
- Analysis of apoptosis induction and the role of NOXA.
- Combination therapy studies with anti-cancer drugs.
- In vivo studies in irradiated and aged mice models.
Main Results:
- Ouabain demonstrates broad senolytic activity, selectively inducing apoptosis in senescent cells.
- Senescent cells are sensitized to ouabain-induced apoptosis, partly via NOXA.
- Cardiac glycosides synergize with anti-cancer drugs to eliminate tumor and senescent cells.
- Ouabain effectively clears senescent cells in vivo after irradiation and in aged mice.
Conclusions:
- Cardiac glycosides, including ouabain, are effective senolytic agents with potential anti-cancer properties.
- Ouabain acts through multiple mechanisms, including sensitization to apoptosis.
- Further exploration of cardiac glycosides for age-related diseases and cancer is warranted.
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