2. Academic Validation
  3. Cardiac glycosides are broad-spectrum senolytics

Cardiac glycosides are broad-spectrum senolytics

  • Nat Metab. 2019 Nov;1(11):1074-1088. doi: 10.1038/s42255-019-0122-z.
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
Affiliations

Affiliations

  • 1 MRC London Institute of Medical Sciences, London, UK.
  • 2 Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK.
  • 3 Division of Chronic Inflammation and Cancer, German Cancer Research Centre, Heidelberg, Germany.
  • 4 Developmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK.
  • 5 Department of Internal Medicine VIII, University Hospital Tübingen, Tübingen, Germany.
  • 6 Department of Physiology I, Institute of Physiology, Eberhard Karls University Tübingen, Tübingen, Germany.
  • 7 Centre for Inflammatory Disease, Imperial College London, Hammersmith Hospital, London, UK.
  • 8 Translational Gastrointestinal Oncology Group, German Consortium for Translational Cancer Research, German Cancer Research Center, Heidelberg, Germany.
  • 9 MRC London Institute of Medical Sciences, London, UK. jesus.gil@imperial.ac.uk.
  • 10 Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK. jesus.gil@imperial.ac.uk.
PMID: 31799499 DOI: 10.1038/s42255-019-0122-z
Abstract

Senescence is a cellular stress response that results in the stable arrest of old, damaged or preneoplastic cells. Oncogene-induced senescence is tumor suppressive but can also exacerbate tumorigenesis through the secretion of pro-inflammatory factors from senescent cells. Drugs that selectively kill senescent cells, termed senolytics, have proved beneficial in animal models of many age-associated diseases. 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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z