The gut microbiota metabolite urolithin A, but not other relevant urolithins, induces p53-dependent cellular senescence in human colon cancer cells

Data will be made available on request.

Detalles Bibliográficos
Autores: Giménez-Bastida, J. A., Ávila-Gálvez, María Ángeles, Espín de Gea, Juan Carlos, González-Sarrías, Antonio
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/411925
Acceso en línea:http://hdl.handle.net/10261/411925
Access Level:acceso abierto
Palabra clave:Urolithins
Colon cancer
Cellular senescence
Phase-II metabolism
ABC transporters
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spelling The gut microbiota metabolite urolithin A, but not other relevant urolithins, induces p53-dependent cellular senescence in human colon cancer cellsGiménez-Bastida, J. A.Ávila-Gálvez, María ÁngelesEspín de Gea, Juan CarlosGonzález-Sarrías, AntonioUrolithinsColon cancerCellular senescencePhase-II metabolismABC transportersData will be made available on request.The promotion of senescence in cancer cells by dietary (poly)phenols gained attention as a promising chemopreventive strategy against colorectal (CRC) and other cancers. Urolithins (Uros) are ellagitannins and ellagic acid-derived gut microbiota metabolites that reach high concentrations in the human colon. They were postulated to be as potential anticancer agents in different CRC models, but their role as promoters of cellular senescence has never been comprehensively evaluated.We evaluated long-term senescent-mediated chemoprevention of physiologically relevant doses of different Uros and representative mixtures of human urolithin metabotypes in human CRC (HCT-116, Caco-2, and HT-29) and non-tumorigenic (CCD18-Co) cell lines. Our results show that Uro-A (but not Uro-C, IsoUro-A, or Uro-B) leads to a dose-dependent anti-clonogenic effect through the increase of the senescence-associated β–galactosidase activity, rather than by reversible cell cycle arrest and(or) apoptosis which require much higher concentrations. Senescence was accompanied by an elevated p53 and p21Cip1/Waf1 expression in HCT-116 cells (p53-wild type), but not in other CRC lines with p53 mutated or non-tumorigenic cells, which suggests that long-term senescence-mediated chemoprevention is a p53-dependent manner. Moreover, the ATP-binding cassette transporters and the phase-II metabolism of Uros limited the induction of senescence, which anticipates lower effects of conjugated Uros against systemic cancers.The study was funded by the projects AGL201564124-R (MINECO, Spain), 201770E081 and 201870I028 (CSIC, Spain). J.A.G.B. is a holder of a Juan de la Cierva contract (IJCI-2016-27633) from the Ministry of Science, Innovation and Universities (Spain).Peer reviewedElsevierMinisterio de Economía y Competitividad (España)Ministerio de Ciencia, Innovación y Universidades (España)Consejo Superior de Investigaciones Científicas (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttp://hdl.handle.net/10261/411925reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO//AGL2015-64124-Rinfo:eu-repo/grantAgreement/MINECO//IJCI-2016-27633The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1016/j.fct.2020.111260https://doi.org/10.1016/j.fct.2020.111260Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4119252026-05-22T06:33:51Z
dc.title.none.fl_str_mv The gut microbiota metabolite urolithin A, but not other relevant urolithins, induces p53-dependent cellular senescence in human colon cancer cells
title The gut microbiota metabolite urolithin A, but not other relevant urolithins, induces p53-dependent cellular senescence in human colon cancer cells
spellingShingle The gut microbiota metabolite urolithin A, but not other relevant urolithins, induces p53-dependent cellular senescence in human colon cancer cells
Giménez-Bastida, J. A.
Urolithins
Colon cancer
Cellular senescence
Phase-II metabolism
ABC transporters
title_short The gut microbiota metabolite urolithin A, but not other relevant urolithins, induces p53-dependent cellular senescence in human colon cancer cells
title_full The gut microbiota metabolite urolithin A, but not other relevant urolithins, induces p53-dependent cellular senescence in human colon cancer cells
title_fullStr The gut microbiota metabolite urolithin A, but not other relevant urolithins, induces p53-dependent cellular senescence in human colon cancer cells
title_full_unstemmed The gut microbiota metabolite urolithin A, but not other relevant urolithins, induces p53-dependent cellular senescence in human colon cancer cells
title_sort The gut microbiota metabolite urolithin A, but not other relevant urolithins, induces p53-dependent cellular senescence in human colon cancer cells
dc.creator.none.fl_str_mv Giménez-Bastida, J. A.
Ávila-Gálvez, María Ángeles
Espín de Gea, Juan Carlos
González-Sarrías, Antonio
author Giménez-Bastida, J. A.
author_facet Giménez-Bastida, J. A.
Ávila-Gálvez, María Ángeles
Espín de Gea, Juan Carlos
González-Sarrías, Antonio
author_role author
author2 Ávila-Gálvez, María Ángeles
Espín de Gea, Juan Carlos
González-Sarrías, Antonio
author2_role author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Consejo Superior de Investigaciones Científicas (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Urolithins
Colon cancer
Cellular senescence
Phase-II metabolism
ABC transporters
topic Urolithins
Colon cancer
Cellular senescence
Phase-II metabolism
ABC transporters
description Data will be made available on request.
publishDate 2020
dc.date.none.fl_str_mv 2020
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/411925
url http://hdl.handle.net/10261/411925
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO//AGL2015-64124-R
info:eu-repo/grantAgreement/MINECO//IJCI-2016-27633
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1016/j.fct.2020.111260
https://doi.org/10.1016/j.fct.2020.111260
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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