Imperial College London
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DrAndrewInnes

Faculty of Medicine, Department of Immunology and Inflammation

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 3313 4017a.innes

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Guerrero:2019:10.1038/s42255-019-0122-z,
author = {Guerrero, A and Herranz, N and Sun, B and Wagner, V and Gallage, S and Guiho, R and Wolter, K and Pombo, J and Irvine, EE and Innes, AJ and Birch, J and Glegola, J and Manshaei, S and Heide, D and Dharmalingam, G and Harbig, J and Olona, A and Behmoaras, J and Dauch, D and Uren, AG and Zender, L and Vernia, S and Martínez-Barbera, JP and Heikenwalder, M and Withers, DJ and Gil, J},
doi = {10.1038/s42255-019-0122-z},
journal = {Nature Metabolism},
pages = {1074--1088},
title = {Cardiac glycosides are broad-spectrum senolytics},
url = {http://dx.doi.org/10.1038/s42255-019-0122-z},
volume = {1},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Senescence is a cellular stress response that results in the stable arrest of old, damaged or pre-neoplastic cells. Oncogene-induced senescence is tumour suppressive but can also exacerbate tumorigenesis through the secretion of proinflammatory factors from senescent cells. Drugs that selectively kill senescent cells, termed ‘senolytics’, have proved beneficial in animal models of many age-associated diseases. In the present study, 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 proapoptotic Bcl-2 family protein NOXA. We demonstrate that cardiac glycosides synergize with anti-cancer drugs to kill tumour cells and eliminate senescent cells that accumulate after irradiation or in old mice. Ouabain also eliminates senescent pre-neoplastic cells. The findings of the present study suggest that cardiac glycosides may be effective anti-cancer drugs by acting through multiple mechanisms. Given the broad range of senescent cells targeted by cardiac glycosides, their use against age-related diseases warrants further exploration.
AU  - Guerrero,A
AU  - Herranz,N
AU  - Sun,B
AU  - Wagner,V
AU  - Gallage,S
AU  - Guiho,R
AU  - Wolter,K
AU  - Pombo,J
AU  - Irvine,EE
AU  - Innes,AJ
AU  - Birch,J
AU  - Glegola,J
AU  - Manshaei,S
AU  - Heide,D
AU  - Dharmalingam,G
AU  - Harbig,J
AU  - Olona,A
AU  - Behmoaras,J
AU  - Dauch,D
AU  - Uren,AG
AU  - Zender,L
AU  - Vernia,S
AU  - Martínez-Barbera,JP
AU  - Heikenwalder,M
AU  - Withers,DJ
AU  - Gil,J
DO  - 10.1038/s42255-019-0122-z
EP  - 1088
PY  - 2019///
SN  - 2522-5812
SP  - 1074
TI  - Cardiac glycosides are broad-spectrum senolytics
T2  - Nature Metabolism
UR  - http://dx.doi.org/10.1038/s42255-019-0122-z
UR  - https://www.nature.com/articles/s42255-019-0122-z
UR  - http://hdl.handle.net/10044/1/74224
VL  - 1
ER  -
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