Silencing peroxiredoxin-2 sensitizes human colorectal cancer cells to ionizing radiation and oxaliplatin

Autores
Cerda, Maria Belen; Lloyd, Rodrigo; Batalla, Milena; Giannoni, Florencia; Casalia, Mariana Laura; Policastro, Lucia Laura
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. Antioxidant enzymes decrease the generation of ionizing radiation (IR)-induced free radicals and therefore are associate to radioresistance. The main goal of this work is to study the involvement of peroxiredoxin-2 (Prx2) in the radio and chemoradiotherapy response in CRC cells in vitro and in vivo. We found that Prx2 oxidation state is associated to differential response to ionizing radiation in CRC cell lines. HCT116 radioresistant CRC cell line have lower ROS levels and a higher monomer/dimer Prx2 ratio, compared to halfway resistant Caco-2 and T84, and radiosensitive LoVo cell line. Constitutive and transient Prx2 silencing in CRC cells increase ROS levels, and most importantly, enhance in vitro radiation sensitivity. In addition, we showed that administration of IR plus oxaliplatin in down regulated Prx2 HCT116 cells has higher citotoxic effect than in control cells. Finally, radiosensitizing effect of Prx2 depletion was confirmed in vivo. These results suggest that Prx2 is an important component in tumoral radiation response, and their inhibition could improve radio and chemoradiotherapy protocols in patients with CRC.
Fil: Cerda, Maria Belen. Comisión Nacional de Energía Atómica; Argentina
Fil: Lloyd, Rodrigo. Comisión Nacional de Energía Atómica; Argentina
Fil: Batalla, Milena. Comisión Nacional de Energía Atómica; Argentina
Fil: Giannoni, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina
Fil: Casalia, Mariana Laura. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Policastro, Lucia Laura. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Colorectal Cancer
Oxaliplatin
Peroxiredoxin 2
Radiation Sensitivity
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/40833

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network_name_str CONICET Digital (CONICET)
spelling Silencing peroxiredoxin-2 sensitizes human colorectal cancer cells to ionizing radiation and oxaliplatinCerda, Maria BelenLloyd, RodrigoBatalla, MilenaGiannoni, FlorenciaCasalia, Mariana LauraPolicastro, Lucia LauraColorectal CancerOxaliplatinPeroxiredoxin 2Radiation Sensitivityhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. Antioxidant enzymes decrease the generation of ionizing radiation (IR)-induced free radicals and therefore are associate to radioresistance. The main goal of this work is to study the involvement of peroxiredoxin-2 (Prx2) in the radio and chemoradiotherapy response in CRC cells in vitro and in vivo. We found that Prx2 oxidation state is associated to differential response to ionizing radiation in CRC cell lines. HCT116 radioresistant CRC cell line have lower ROS levels and a higher monomer/dimer Prx2 ratio, compared to halfway resistant Caco-2 and T84, and radiosensitive LoVo cell line. Constitutive and transient Prx2 silencing in CRC cells increase ROS levels, and most importantly, enhance in vitro radiation sensitivity. In addition, we showed that administration of IR plus oxaliplatin in down regulated Prx2 HCT116 cells has higher citotoxic effect than in control cells. Finally, radiosensitizing effect of Prx2 depletion was confirmed in vivo. These results suggest that Prx2 is an important component in tumoral radiation response, and their inhibition could improve radio and chemoradiotherapy protocols in patients with CRC.Fil: Cerda, Maria Belen. Comisión Nacional de Energía Atómica; ArgentinaFil: Lloyd, Rodrigo. Comisión Nacional de Energía Atómica; ArgentinaFil: Batalla, Milena. Comisión Nacional de Energía Atómica; ArgentinaFil: Giannoni, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Casalia, Mariana Laura. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Policastro, Lucia Laura. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier Ireland2017-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/40833Cerda, Maria Belen; Lloyd, Rodrigo; Batalla, Milena; Giannoni, Florencia; Casalia, Mariana Laura; et al.; Silencing peroxiredoxin-2 sensitizes human colorectal cancer cells to ionizing radiation and oxaliplatin; Elsevier Ireland; Cancer Letters; 388; 3-2017; 312-3190304-3835CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.canlet.2016.12.009info:eu-repo/semantics/altIdentifier/url/http://www.cancerletters.info/article/S0304-3835(16)30762-5/fulltextinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:40:48Zoai:ri.conicet.gov.ar:11336/40833instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:40:48.36CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Silencing peroxiredoxin-2 sensitizes human colorectal cancer cells to ionizing radiation and oxaliplatin
title Silencing peroxiredoxin-2 sensitizes human colorectal cancer cells to ionizing radiation and oxaliplatin
spellingShingle Silencing peroxiredoxin-2 sensitizes human colorectal cancer cells to ionizing radiation and oxaliplatin
Cerda, Maria Belen
Colorectal Cancer
Oxaliplatin
Peroxiredoxin 2
Radiation Sensitivity
title_short Silencing peroxiredoxin-2 sensitizes human colorectal cancer cells to ionizing radiation and oxaliplatin
title_full Silencing peroxiredoxin-2 sensitizes human colorectal cancer cells to ionizing radiation and oxaliplatin
title_fullStr Silencing peroxiredoxin-2 sensitizes human colorectal cancer cells to ionizing radiation and oxaliplatin
title_full_unstemmed Silencing peroxiredoxin-2 sensitizes human colorectal cancer cells to ionizing radiation and oxaliplatin
title_sort Silencing peroxiredoxin-2 sensitizes human colorectal cancer cells to ionizing radiation and oxaliplatin
dc.creator.none.fl_str_mv Cerda, Maria Belen
Lloyd, Rodrigo
Batalla, Milena
Giannoni, Florencia
Casalia, Mariana Laura
Policastro, Lucia Laura
author Cerda, Maria Belen
author_facet Cerda, Maria Belen
Lloyd, Rodrigo
Batalla, Milena
Giannoni, Florencia
Casalia, Mariana Laura
Policastro, Lucia Laura
author_role author
author2 Lloyd, Rodrigo
Batalla, Milena
Giannoni, Florencia
Casalia, Mariana Laura
Policastro, Lucia Laura
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Colorectal Cancer
Oxaliplatin
Peroxiredoxin 2
Radiation Sensitivity
topic Colorectal Cancer
Oxaliplatin
Peroxiredoxin 2
Radiation Sensitivity
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. Antioxidant enzymes decrease the generation of ionizing radiation (IR)-induced free radicals and therefore are associate to radioresistance. The main goal of this work is to study the involvement of peroxiredoxin-2 (Prx2) in the radio and chemoradiotherapy response in CRC cells in vitro and in vivo. We found that Prx2 oxidation state is associated to differential response to ionizing radiation in CRC cell lines. HCT116 radioresistant CRC cell line have lower ROS levels and a higher monomer/dimer Prx2 ratio, compared to halfway resistant Caco-2 and T84, and radiosensitive LoVo cell line. Constitutive and transient Prx2 silencing in CRC cells increase ROS levels, and most importantly, enhance in vitro radiation sensitivity. In addition, we showed that administration of IR plus oxaliplatin in down regulated Prx2 HCT116 cells has higher citotoxic effect than in control cells. Finally, radiosensitizing effect of Prx2 depletion was confirmed in vivo. These results suggest that Prx2 is an important component in tumoral radiation response, and their inhibition could improve radio and chemoradiotherapy protocols in patients with CRC.
Fil: Cerda, Maria Belen. Comisión Nacional de Energía Atómica; Argentina
Fil: Lloyd, Rodrigo. Comisión Nacional de Energía Atómica; Argentina
Fil: Batalla, Milena. Comisión Nacional de Energía Atómica; Argentina
Fil: Giannoni, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina
Fil: Casalia, Mariana Laura. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Policastro, Lucia Laura. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. Antioxidant enzymes decrease the generation of ionizing radiation (IR)-induced free radicals and therefore are associate to radioresistance. The main goal of this work is to study the involvement of peroxiredoxin-2 (Prx2) in the radio and chemoradiotherapy response in CRC cells in vitro and in vivo. We found that Prx2 oxidation state is associated to differential response to ionizing radiation in CRC cell lines. HCT116 radioresistant CRC cell line have lower ROS levels and a higher monomer/dimer Prx2 ratio, compared to halfway resistant Caco-2 and T84, and radiosensitive LoVo cell line. Constitutive and transient Prx2 silencing in CRC cells increase ROS levels, and most importantly, enhance in vitro radiation sensitivity. In addition, we showed that administration of IR plus oxaliplatin in down regulated Prx2 HCT116 cells has higher citotoxic effect than in control cells. Finally, radiosensitizing effect of Prx2 depletion was confirmed in vivo. These results suggest that Prx2 is an important component in tumoral radiation response, and their inhibition could improve radio and chemoradiotherapy protocols in patients with CRC.
publishDate 2017
dc.date.none.fl_str_mv 2017-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/40833
Cerda, Maria Belen; Lloyd, Rodrigo; Batalla, Milena; Giannoni, Florencia; Casalia, Mariana Laura; et al.; Silencing peroxiredoxin-2 sensitizes human colorectal cancer cells to ionizing radiation and oxaliplatin; Elsevier Ireland; Cancer Letters; 388; 3-2017; 312-319
0304-3835
CONICET Digital
CONICET
url http://hdl.handle.net/11336/40833
identifier_str_mv Cerda, Maria Belen; Lloyd, Rodrigo; Batalla, Milena; Giannoni, Florencia; Casalia, Mariana Laura; et al.; Silencing peroxiredoxin-2 sensitizes human colorectal cancer cells to ionizing radiation and oxaliplatin; Elsevier Ireland; Cancer Letters; 388; 3-2017; 312-319
0304-3835
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.canlet.2016.12.009
info:eu-repo/semantics/altIdentifier/url/http://www.cancerletters.info/article/S0304-3835(16)30762-5/fulltext
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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