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Cardiac glycosides are broad-spectrum senolytics
Ana Guerrero 1 2, Nicolás Herranz 1 2, Bin Sun 1 2, Verena Wagner 1 2, Suchira Gallage 1 2 3, Romain Guiho 4, Katharina Wolter 5 6, Joaquim Pombo 1 2, Elaine E Irvine 1 2, Andrew J Innes 1 2, Jodie Birch 1 2, Justyna Glegola 1 2, Saba Manshaei 4, Danijela Heide 3, Gopuraja Dharmalingam 1 2, Jule Harbig 5 6, Antoni Olona 7, Jacques Behmoaras 7, Daniel Dauch 5 6, Anthony G Uren 1 2, Lars Zender 5 6 8, Santiago Vernia 1 2, Juan Pedro Martínez-Barbera 4, Mathias Heikenwalder 3, Dominic J Withers 1 2, Jesús Gil 9 10
Abstract:
...Here, we show that the cardiac glycoside, ouabain, is a senolytic agent with broad activity. Senescent cells are sensitized to ouabain-induced apoptosis, a process mediated in part by induction of the pro-apoptotic Bcl2-family protein NOXA. We show that cardiac glycosides synergize with anti-cancer drugs to kill tumor cells and eliminate senescent cells that accumulate after irradiation or in old mice. Ouabain also eliminates senescent preneoplastic cells. Our findings suggest that cardiac glycosides may be effective anti-cancer drugs by acting through multiple mechanism. Given the broad range of senescent cells targeted by cardiac glycosides their use against age-related diseases warrants further exploration.
PMID: 31799499
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887543/
SENS Approach:
