RAC3 influences the chemoresistance of colon cancer cells through autophagy and apoptosis inhibition

Autores
Rubio, Maria Fernanda; Lira, María Cecilia; Rosa, Francisco Damián; Sambresqui, Adrián Dario; Salazar Güemes, María Cecilia; Costas, Monica Alejandra
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: RAC3 coactivator overexpression has been implicated in tumorigenesis, contributing to inhibition ofapoptosis and autophagy. Both mechanisms are involved in resistance to treatment with chemotherapeutic agents.The aim of this study was to investigate its role in chemoresistance of colorectal cancer.Methods: The sensitivity to 5-fluorouracil and oxaliplatin in colon cancer cells HT-29, HCT 116 and Lovo cell lines,expressing high or low natural levels of RAC3, was investigated using viability assays.Results: In HCT 116 cells, we found that although 5-fluorouracil was a poor inducer of apoptosis, autophagy wasstrongly induced, while oxaliplatin has shown a similar ability to induce both of them. However, in HCT 116 cellsexpressing a short hairpin RNA for RAC3, we found an increased sensitivity to both drugs if it is compared with controlcells. 5-Fluorouracil and oxaliplatin treatment lead to an enhanced caspase 3-dependent apoptosis and produce anincrease of autophagy. In addition, both process have shown to be trigged faster than in control cells, starting earlierafter stimulation.Conclusions: Our results suggest that RAC3 expression levels influence the sensitivity to chemotherapeutic drugs.Therefore, the knowledge of RAC3 expression levels in tumoral samples could be an important contribution to designnew improved therapeutic strategies in the future.
Fil: Rubio, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Lira, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Rosa, Francisco Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Sambresqui, Adrián Dario. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Salazar Güemes, María Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Costas, Monica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Materia
Colorectal Cancer
Rac3
Chemoresistance
Apoptosis
Autophagy
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/47231
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/47231
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling RAC3 influences the chemoresistance of colon cancer cells through autophagy and apoptosis inhibitionRubio, Maria FernandaLira, María CeciliaRosa, Francisco DamiánSambresqui, Adrián DarioSalazar Güemes, María CeciliaCostas, Monica AlejandraColorectal CancerRac3ChemoresistanceApoptosisAutophagyhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Background: RAC3 coactivator overexpression has been implicated in tumorigenesis, contributing to inhibition ofapoptosis and autophagy. Both mechanisms are involved in resistance to treatment with chemotherapeutic agents.The aim of this study was to investigate its role in chemoresistance of colorectal cancer.Methods: The sensitivity to 5-fluorouracil and oxaliplatin in colon cancer cells HT-29, HCT 116 and Lovo cell lines,expressing high or low natural levels of RAC3, was investigated using viability assays.Results: In HCT 116 cells, we found that although 5-fluorouracil was a poor inducer of apoptosis, autophagy wasstrongly induced, while oxaliplatin has shown a similar ability to induce both of them. However, in HCT 116 cellsexpressing a short hairpin RNA for RAC3, we found an increased sensitivity to both drugs if it is compared with controlcells. 5-Fluorouracil and oxaliplatin treatment lead to an enhanced caspase 3-dependent apoptosis and produce anincrease of autophagy. In addition, both process have shown to be trigged faster than in control cells, starting earlierafter stimulation.Conclusions: Our results suggest that RAC3 expression levels influence the sensitivity to chemotherapeutic drugs.Therefore, the knowledge of RAC3 expression levels in tumoral samples could be an important contribution to designnew improved therapeutic strategies in the future.Fil: Rubio, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Lira, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Rosa, Francisco Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Sambresqui, Adrián Dario. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Salazar Güemes, María Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Costas, Monica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaBioMed Central2017-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/47231Rubio, Maria Fernanda; Lira, María Cecilia; Rosa, Francisco Damián; Sambresqui, Adrián Dario; Salazar Güemes, María Cecilia; et al.; RAC3 influences the chemoresistance of colon cancer cells through autophagy and apoptosis inhibition; BioMed Central; Cancer Cell International; 17; 1; 11-2017; 1-171475-2867CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://cancerci.biomedcentral.com/articles/10.1186/s12935-017-0483-xinfo:eu-repo/semantics/altIdentifier/doi/10.1186/s12935-017-0483-xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:01:13Zoai:ri.conicet.gov.ar:11336/47231instacron: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 10:01:13.696CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv RAC3 influences the chemoresistance of colon cancer cells through autophagy and apoptosis inhibition
title RAC3 influences the chemoresistance of colon cancer cells through autophagy and apoptosis inhibition
spellingShingle RAC3 influences the chemoresistance of colon cancer cells through autophagy and apoptosis inhibition
Rubio, Maria Fernanda
Colorectal Cancer
Rac3
Chemoresistance
Apoptosis
Autophagy
title_short RAC3 influences the chemoresistance of colon cancer cells through autophagy and apoptosis inhibition
title_full RAC3 influences the chemoresistance of colon cancer cells through autophagy and apoptosis inhibition
title_fullStr RAC3 influences the chemoresistance of colon cancer cells through autophagy and apoptosis inhibition
title_full_unstemmed RAC3 influences the chemoresistance of colon cancer cells through autophagy and apoptosis inhibition
title_sort RAC3 influences the chemoresistance of colon cancer cells through autophagy and apoptosis inhibition
dc.creator.none.fl_str_mv Rubio, Maria Fernanda
Lira, María Cecilia
Rosa, Francisco Damián
Sambresqui, Adrián Dario
Salazar Güemes, María Cecilia
Costas, Monica Alejandra
author Rubio, Maria Fernanda
author_facet Rubio, Maria Fernanda
Lira, María Cecilia
Rosa, Francisco Damián
Sambresqui, Adrián Dario
Salazar Güemes, María Cecilia
Costas, Monica Alejandra
author_role author
author2 Lira, María Cecilia
Rosa, Francisco Damián
Sambresqui, Adrián Dario
Salazar Güemes, María Cecilia
Costas, Monica Alejandra
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Colorectal Cancer
Rac3
Chemoresistance
Apoptosis
Autophagy
topic Colorectal Cancer
Rac3
Chemoresistance
Apoptosis
Autophagy
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: RAC3 coactivator overexpression has been implicated in tumorigenesis, contributing to inhibition ofapoptosis and autophagy. Both mechanisms are involved in resistance to treatment with chemotherapeutic agents.The aim of this study was to investigate its role in chemoresistance of colorectal cancer.Methods: The sensitivity to 5-fluorouracil and oxaliplatin in colon cancer cells HT-29, HCT 116 and Lovo cell lines,expressing high or low natural levels of RAC3, was investigated using viability assays.Results: In HCT 116 cells, we found that although 5-fluorouracil was a poor inducer of apoptosis, autophagy wasstrongly induced, while oxaliplatin has shown a similar ability to induce both of them. However, in HCT 116 cellsexpressing a short hairpin RNA for RAC3, we found an increased sensitivity to both drugs if it is compared with controlcells. 5-Fluorouracil and oxaliplatin treatment lead to an enhanced caspase 3-dependent apoptosis and produce anincrease of autophagy. In addition, both process have shown to be trigged faster than in control cells, starting earlierafter stimulation.Conclusions: Our results suggest that RAC3 expression levels influence the sensitivity to chemotherapeutic drugs.Therefore, the knowledge of RAC3 expression levels in tumoral samples could be an important contribution to designnew improved therapeutic strategies in the future.
Fil: Rubio, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Lira, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Rosa, Francisco Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Sambresqui, Adrián Dario. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Salazar Güemes, María Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Costas, Monica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
description Background: RAC3 coactivator overexpression has been implicated in tumorigenesis, contributing to inhibition ofapoptosis and autophagy. Both mechanisms are involved in resistance to treatment with chemotherapeutic agents.The aim of this study was to investigate its role in chemoresistance of colorectal cancer.Methods: The sensitivity to 5-fluorouracil and oxaliplatin in colon cancer cells HT-29, HCT 116 and Lovo cell lines,expressing high or low natural levels of RAC3, was investigated using viability assays.Results: In HCT 116 cells, we found that although 5-fluorouracil was a poor inducer of apoptosis, autophagy wasstrongly induced, while oxaliplatin has shown a similar ability to induce both of them. However, in HCT 116 cellsexpressing a short hairpin RNA for RAC3, we found an increased sensitivity to both drugs if it is compared with controlcells. 5-Fluorouracil and oxaliplatin treatment lead to an enhanced caspase 3-dependent apoptosis and produce anincrease of autophagy. In addition, both process have shown to be trigged faster than in control cells, starting earlierafter stimulation.Conclusions: Our results suggest that RAC3 expression levels influence the sensitivity to chemotherapeutic drugs.Therefore, the knowledge of RAC3 expression levels in tumoral samples could be an important contribution to designnew improved therapeutic strategies in the future.
publishDate 2017
dc.date.none.fl_str_mv 2017-11
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/11336/47231
Rubio, Maria Fernanda; Lira, María Cecilia; Rosa, Francisco Damián; Sambresqui, Adrián Dario; Salazar Güemes, María Cecilia; et al.; RAC3 influences the chemoresistance of colon cancer cells through autophagy and apoptosis inhibition; BioMed Central; Cancer Cell International; 17; 1; 11-2017; 1-17
1475-2867
CONICET Digital
CONICET
url http://hdl.handle.net/11336/47231
identifier_str_mv Rubio, Maria Fernanda; Lira, María Cecilia; Rosa, Francisco Damián; Sambresqui, Adrián Dario; Salazar Güemes, María Cecilia; et al.; RAC3 influences the chemoresistance of colon cancer cells through autophagy and apoptosis inhibition; BioMed Central; Cancer Cell International; 17; 1; 11-2017; 1-17
1475-2867
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://cancerci.biomedcentral.com/articles/10.1186/s12935-017-0483-x
info:eu-repo/semantics/altIdentifier/doi/10.1186/s12935-017-0483-x
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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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score 13.070432

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