Resminostat induces changes in epithelial plasticity of hepatocellular carcinoma cells and sensitizes them to sorafenib-induced apoptosis

Resminostat, a novel class I, IIb, and IV histone deacetylase inhibitor, was studied in advanced hepatocellular carcinoma (HCC) patients after relapse to sorafenib (SHELTER study). In this phase I/II clinical trial, combination of sorafenib and resminostat was safe and showed early signs of efficacy...

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Autores: Soukupova, Jitka, Bertran Rodríguez, Esther, Peñuelas Haro, Irene, Urdiroz Urricelqui, Uxue, Borgman, Matthias, Kohlhof, Hella, Fabregat Romero, Isabel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/178703
Acceso en línea:https://hdl.handle.net/2445/178703
Access Level:acceso abierto
Palabra clave:Hepatologia
Càncer
Apoptosi
Hepatology
Cancer
Apoptosis
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spelling Resminostat induces changes in epithelial plasticity of hepatocellular carcinoma cells and sensitizes them to sorafenib-induced apoptosisSoukupova, JitkaBertran Rodríguez, EstherPeñuelas Haro, IreneUrdiroz Urricelqui, UxueBorgman, MatthiasKohlhof, HellaFabregat Romero, IsabelHepatologiaCàncerApoptosiHepatologyCancerApoptosisResminostat, a novel class I, IIb, and IV histone deacetylase inhibitor, was studied in advanced hepatocellular carcinoma (HCC) patients after relapse to sorafenib (SHELTER study). In this phase I/II clinical trial, combination of sorafenib and resminostat was safe and showed early signs of efficacy. However, the molecular mechanisms behind this synergism have not been explored yet. In this work, we aimed to analyze whether resminostat regulates epithelial-mesenchymal and stemness phenotype as a mechanism of sensitization to sorafenib. Three HCC cell lines with differences in their epithelial/mesenchymal characteristics were treated with resminostat and sorafenib alone, or in combination. Resminostat prevented growth and induced cell death in the HCC cells, in a time and dose dependent manner. A collaborative effect between resminostat and sorafenib was detected in the mesenchymal HCC cells, which were insensitive to sorafenib-induced apoptosis. Expression of mesenchymal-related genes was decreased in resminostat-treated HCC cells, concomitant with an increase in epithelial-related gene expression, organized tight junctions and reduced invasive growth. Moreover, resminostat down-regulated CD44 expression, coincident with decreased capacity to form colonies at low cell density.Impact Journals2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/178703Articles publicats en revistes (Ciències Fisiològiques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.18632/oncotarget.22775Oncotarget, 2017, vol. 8, num. 66, p. 110367-110379https://doi.org/10.18632/oncotarget.22775info:eu-repo/grantAgreement/EC/FP7/316549cc-by (c) Soukupova, Jitka et al., 2017https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1787032026-05-27T06:46:51Z
dc.title.none.fl_str_mv Resminostat induces changes in epithelial plasticity of hepatocellular carcinoma cells and sensitizes them to sorafenib-induced apoptosis
title Resminostat induces changes in epithelial plasticity of hepatocellular carcinoma cells and sensitizes them to sorafenib-induced apoptosis
spellingShingle Resminostat induces changes in epithelial plasticity of hepatocellular carcinoma cells and sensitizes them to sorafenib-induced apoptosis
Soukupova, Jitka
Hepatologia
Càncer
Apoptosi
Hepatology
Cancer
Apoptosis
title_short Resminostat induces changes in epithelial plasticity of hepatocellular carcinoma cells and sensitizes them to sorafenib-induced apoptosis
title_full Resminostat induces changes in epithelial plasticity of hepatocellular carcinoma cells and sensitizes them to sorafenib-induced apoptosis
title_fullStr Resminostat induces changes in epithelial plasticity of hepatocellular carcinoma cells and sensitizes them to sorafenib-induced apoptosis
title_full_unstemmed Resminostat induces changes in epithelial plasticity of hepatocellular carcinoma cells and sensitizes them to sorafenib-induced apoptosis
title_sort Resminostat induces changes in epithelial plasticity of hepatocellular carcinoma cells and sensitizes them to sorafenib-induced apoptosis
dc.creator.none.fl_str_mv Soukupova, Jitka
Bertran Rodríguez, Esther
Peñuelas Haro, Irene
Urdiroz Urricelqui, Uxue
Borgman, Matthias
Kohlhof, Hella
Fabregat Romero, Isabel
author Soukupova, Jitka
author_facet Soukupova, Jitka
Bertran Rodríguez, Esther
Peñuelas Haro, Irene
Urdiroz Urricelqui, Uxue
Borgman, Matthias
Kohlhof, Hella
Fabregat Romero, Isabel
author_role author
author2 Bertran Rodríguez, Esther
Peñuelas Haro, Irene
Urdiroz Urricelqui, Uxue
Borgman, Matthias
Kohlhof, Hella
Fabregat Romero, Isabel
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Hepatologia
Càncer
Apoptosi
Hepatology
Cancer
Apoptosis
topic Hepatologia
Càncer
Apoptosi
Hepatology
Cancer
Apoptosis
description Resminostat, a novel class I, IIb, and IV histone deacetylase inhibitor, was studied in advanced hepatocellular carcinoma (HCC) patients after relapse to sorafenib (SHELTER study). In this phase I/II clinical trial, combination of sorafenib and resminostat was safe and showed early signs of efficacy. However, the molecular mechanisms behind this synergism have not been explored yet. In this work, we aimed to analyze whether resminostat regulates epithelial-mesenchymal and stemness phenotype as a mechanism of sensitization to sorafenib. Three HCC cell lines with differences in their epithelial/mesenchymal characteristics were treated with resminostat and sorafenib alone, or in combination. Resminostat prevented growth and induced cell death in the HCC cells, in a time and dose dependent manner. A collaborative effect between resminostat and sorafenib was detected in the mesenchymal HCC cells, which were insensitive to sorafenib-induced apoptosis. Expression of mesenchymal-related genes was decreased in resminostat-treated HCC cells, concomitant with an increase in epithelial-related gene expression, organized tight junctions and reduced invasive growth. Moreover, resminostat down-regulated CD44 expression, coincident with decreased capacity to form colonies at low cell density.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/178703
url https://hdl.handle.net/2445/178703
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.18632/oncotarget.22775
Oncotarget, 2017, vol. 8, num. 66, p. 110367-110379
https://doi.org/10.18632/oncotarget.22775
info:eu-repo/grantAgreement/EC/FP7/316549
dc.rights.none.fl_str_mv cc-by (c) Soukupova, Jitka et al., 2017
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Soukupova, Jitka et al., 2017
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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