Evidence map›Paper›PMID 31799499›Full record

ArticleNature metabolism2019

Cardiac glycosides are broad-spectrum senolytics.

Ana Guerrero, Nicolás Herranz, Bin Sun, Verena Wagner, Suchira Gallage, Romain Guiho, Katharina Wolter, Joaquim Pombo, Elaine E Irvine, Andrew J Innes and 16 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 214 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
214citing papers in PubMed, 1 pooled it
25.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

214 citing papers in PubMed, 1 synthesis or guideline pooled it, 340 citations in OpenAlex.

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154 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 6 institutions in 2 countries.

Ana GuerreroMRC London Institute of Medical Sciences, London, UK.
Nicolás HerranzMRC London Institute of Medical Sciences, London, UK.
Bin SunMRC London Institute of Medical Sciences, London, UK.ORCID http://orcid.org/0000-0002-8963-4100
Verena WagnerMRC London Institute of Medical Sciences, London, UK.
Suchira GallageMRC London Institute of Medical Sciences, London, UK.ORCID http://orcid.org/0000-0002-1956-3597
Romain GuihoDevelopmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK.
Katharina WolterDepartment of Internal Medicine VIII, University Hospital Tübingen, Tübingen, Germany.
Joaquim PomboMRC London Institute of Medical Sciences, London, UK.
Elaine E IrvineMRC London Institute of Medical Sciences, London, UK.
Andrew J InnesMRC London Institute of Medical Sciences, London, UK.ORCID http://orcid.org/0000-0003-0918-8882
Jodie BirchMRC London Institute of Medical Sciences, London, UK.ORCID http://orcid.org/0000-0003-1727-1125
Justyna GlegolaMRC London Institute of Medical Sciences, London, UK.
Saba ManshaeiDevelopmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK.
Danijela HeideDivision of Chronic Inflammation and Cancer, German Cancer Research Centre, Heidelberg, Germany.
Gopuraja DharmalingamMRC London Institute of Medical Sciences, London, UK.
Jule HarbigDepartment of Internal Medicine VIII, University Hospital Tübingen, Tübingen, Germany.
Antoni OlonaCentre for Inflammatory Disease, Imperial College London, Hammersmith Hospital, London, UK.
Jacques BehmoarasCentre for Inflammatory Disease, Imperial College London, Hammersmith Hospital, London, UK.
Daniel DauchDepartment of Internal Medicine VIII, University Hospital Tübingen, Tübingen, Germany.
Anthony G UrenMRC London Institute of Medical Sciences, London, UK.
Lars ZenderDepartment of Internal Medicine VIII, University Hospital Tübingen, Tübingen, Germany.
Santiago VerniaMRC London Institute of Medical Sciences, London, UK.
Juan Pedro Martínez-BarberaDevelopmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK.ORCID http://orcid.org/0000-0002-5292-7276
Mathias HeikenwalderDivision of Chronic Inflammation and Cancer, German Cancer Research Centre, Heidelberg, Germany.
Dominic J WithersMRC London Institute of Medical Sciences, London, UK.ORCID http://orcid.org/0000-0002-8009-7521
Jesús GilMRC London Institute of Medical Sciences, London, UK. jesus.gil@imperial.ac.uk.ORCID http://orcid.org/0000-0002-4303-6260
MRC London Institute of Medical Sciences · GBGerman Cancer Research Center · DEUniversity Children's Hospital Tübingen · DEUniversity College London · GBHammersmith Hospital · GBNIHR Imperial Biomedical Research Centre · GB

Funding

Cancer Research UK 27727Cancer Research UK 28647Medical Research Council MC-A654-5QB40Medical Research Council MC_U120085810Medical Research Council MC_U120097114Medical Research Council MC_UP_1102/18Medical Research Council MC_UP_A652_1001Medical Research Council MR/M000125/1Medical Research Council MR/M004716/1Medical Research Council MR/N01121X/1Wellcome TrustWellcome Trust 098565Worldwide Cancer Research 18-0215
6 · The paper itself

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.

Indexed as

AnimalsAntineoplastic AgentsApoptosisCardiac GlycosidesCellular SenescenceHumansMiceOuabainQuercetinRatsAntineoplastic AgentsCardiac GlycosidesOuabainQuercetin

Identifiers

PMID31799499
PMCPMC6887543
OpenAlexW2980638238

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.