Suppression of cancer growth by non-viral gene therapy based on a novel reactive oxygen species-responsive promoter

Autores
Policastro, Lucia Laura; Ibañez, Irene Laura; Duran, Hebe Alicia; Soria, Ramiro Gaston; Gottifredi, Vanesa; Podhajcer, Osvaldo Luis
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Increased reactive oxygen species (ROS) production has been reported as a distinctive feature of different pathologies including cancer. Therefore, we assessed whether increased ROS production in the cancer microenvironment could be selectively exploited to develop a selective anti-cancer therapy. For this purpose we constructed a novel chimeric promoter, based on a ROS-response motif located in the VEGF gene promoter placed, in turn, downstream of a second ROS-response motif obtained from the early growth response 1 (Egr-1) gene promoter. The activity of the chimeric promoter was largely dependent on variations in intracellular ROS levels and showed a high inducible response to exogenous H2O2. Transient expression of the thymidine kinase gene (TK) driven by the chimeric promoter, followed by gancyclovir administration, inhibited human colorectal cancer and melanoma cell growth in vitro and in vivo. Moreover, electrotransfer of the TK gene followed by gancyclovir (GCV) administration exerted a potent therapeutic effect on established tumors. This response was improved when combined with chemotherapeutic drugs. Thus, we show for the first time that a distinctive pro-oxidant state can be used to develop new selective gene therapeutics for cancer.
Fil: Policastro, Lucia Laura. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Ibañez, Irene Laura. Comisión Nacional de Energía Atómica; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina
Fil: Duran, Hebe Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina
Fil: Soria, Ramiro Gaston. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Gottifredi, Vanesa. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Podhajcer, Osvaldo Luis. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Materia
Reactive Oxygen Species
Cancer
Gene Therapy
Chimeric Promoter
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:11336/25652
Acceder
id CONICETDig_63aa8cad7566c8899391b2bb188447d0
oai_identifier_str oai:ri.conicet.gov.ar:11336/25652
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Suppression of cancer growth by non-viral gene therapy based on a novel reactive oxygen species-responsive promoterPolicastro, Lucia LauraIbañez, Irene LauraDuran, Hebe AliciaSoria, Ramiro GastonGottifredi, VanesaPodhajcer, Osvaldo LuisReactive Oxygen SpeciesCancerGene TherapyChimeric Promoterhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Increased reactive oxygen species (ROS) production has been reported as a distinctive feature of different pathologies including cancer. Therefore, we assessed whether increased ROS production in the cancer microenvironment could be selectively exploited to develop a selective anti-cancer therapy. For this purpose we constructed a novel chimeric promoter, based on a ROS-response motif located in the VEGF gene promoter placed, in turn, downstream of a second ROS-response motif obtained from the early growth response 1 (Egr-1) gene promoter. The activity of the chimeric promoter was largely dependent on variations in intracellular ROS levels and showed a high inducible response to exogenous H2O2. Transient expression of the thymidine kinase gene (TK) driven by the chimeric promoter, followed by gancyclovir administration, inhibited human colorectal cancer and melanoma cell growth in vitro and in vivo. Moreover, electrotransfer of the TK gene followed by gancyclovir (GCV) administration exerted a potent therapeutic effect on established tumors. This response was improved when combined with chemotherapeutic drugs. Thus, we show for the first time that a distinctive pro-oxidant state can be used to develop new selective gene therapeutics for cancer.Fil: Policastro, Lucia Laura. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Ibañez, Irene Laura. Comisión Nacional de Energía Atómica; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; ArgentinaFil: Duran, Hebe Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; ArgentinaFil: Soria, Ramiro Gaston. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Gottifredi, Vanesa. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Podhajcer, Osvaldo Luis. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaCell Press2009-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/25652Policastro, Lucia Laura; Ibañez, Irene Laura; Duran, Hebe Alicia; Soria, Ramiro Gaston; Gottifredi, Vanesa; et al.; Suppression of cancer growth by non-viral gene therapy based on a novel reactive oxygen species-responsive promoter; Cell Press; Molecular Therapy (print); 17; 8; 8-2009; 1355-13641525-0016CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(16)31856-1info:eu-repo/semantics/altIdentifier/doi/10.1038/mt.2009.103info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:37:32Zoai:ri.conicet.gov.ar:11336/25652instacron: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 10:37:32.676CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Suppression of cancer growth by non-viral gene therapy based on a novel reactive oxygen species-responsive promoter
title Suppression of cancer growth by non-viral gene therapy based on a novel reactive oxygen species-responsive promoter
spellingShingle Suppression of cancer growth by non-viral gene therapy based on a novel reactive oxygen species-responsive promoter
Policastro, Lucia Laura
Reactive Oxygen Species
Cancer
Gene Therapy
Chimeric Promoter
title_short Suppression of cancer growth by non-viral gene therapy based on a novel reactive oxygen species-responsive promoter
title_full Suppression of cancer growth by non-viral gene therapy based on a novel reactive oxygen species-responsive promoter
title_fullStr Suppression of cancer growth by non-viral gene therapy based on a novel reactive oxygen species-responsive promoter
title_full_unstemmed Suppression of cancer growth by non-viral gene therapy based on a novel reactive oxygen species-responsive promoter
title_sort Suppression of cancer growth by non-viral gene therapy based on a novel reactive oxygen species-responsive promoter
dc.creator.none.fl_str_mv Policastro, Lucia Laura
Ibañez, Irene Laura
Duran, Hebe Alicia
Soria, Ramiro Gaston
Gottifredi, Vanesa
Podhajcer, Osvaldo Luis
author Policastro, Lucia Laura
author_facet Policastro, Lucia Laura
Ibañez, Irene Laura
Duran, Hebe Alicia
Soria, Ramiro Gaston
Gottifredi, Vanesa
Podhajcer, Osvaldo Luis
author_role author
author2 Ibañez, Irene Laura
Duran, Hebe Alicia
Soria, Ramiro Gaston
Gottifredi, Vanesa
Podhajcer, Osvaldo Luis
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Reactive Oxygen Species
Cancer
Gene Therapy
Chimeric Promoter
topic Reactive Oxygen Species
Cancer
Gene Therapy
Chimeric Promoter
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Increased reactive oxygen species (ROS) production has been reported as a distinctive feature of different pathologies including cancer. Therefore, we assessed whether increased ROS production in the cancer microenvironment could be selectively exploited to develop a selective anti-cancer therapy. For this purpose we constructed a novel chimeric promoter, based on a ROS-response motif located in the VEGF gene promoter placed, in turn, downstream of a second ROS-response motif obtained from the early growth response 1 (Egr-1) gene promoter. The activity of the chimeric promoter was largely dependent on variations in intracellular ROS levels and showed a high inducible response to exogenous H2O2. Transient expression of the thymidine kinase gene (TK) driven by the chimeric promoter, followed by gancyclovir administration, inhibited human colorectal cancer and melanoma cell growth in vitro and in vivo. Moreover, electrotransfer of the TK gene followed by gancyclovir (GCV) administration exerted a potent therapeutic effect on established tumors. This response was improved when combined with chemotherapeutic drugs. Thus, we show for the first time that a distinctive pro-oxidant state can be used to develop new selective gene therapeutics for cancer.
Fil: Policastro, Lucia Laura. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Ibañez, Irene Laura. Comisión Nacional de Energía Atómica; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina
Fil: Duran, Hebe Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina
Fil: Soria, Ramiro Gaston. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Gottifredi, Vanesa. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Podhajcer, Osvaldo Luis. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
description Increased reactive oxygen species (ROS) production has been reported as a distinctive feature of different pathologies including cancer. Therefore, we assessed whether increased ROS production in the cancer microenvironment could be selectively exploited to develop a selective anti-cancer therapy. For this purpose we constructed a novel chimeric promoter, based on a ROS-response motif located in the VEGF gene promoter placed, in turn, downstream of a second ROS-response motif obtained from the early growth response 1 (Egr-1) gene promoter. The activity of the chimeric promoter was largely dependent on variations in intracellular ROS levels and showed a high inducible response to exogenous H2O2. Transient expression of the thymidine kinase gene (TK) driven by the chimeric promoter, followed by gancyclovir administration, inhibited human colorectal cancer and melanoma cell growth in vitro and in vivo. Moreover, electrotransfer of the TK gene followed by gancyclovir (GCV) administration exerted a potent therapeutic effect on established tumors. This response was improved when combined with chemotherapeutic drugs. Thus, we show for the first time that a distinctive pro-oxidant state can be used to develop new selective gene therapeutics for cancer.
publishDate 2009
dc.date.none.fl_str_mv 2009-08
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/11336/25652
Policastro, Lucia Laura; Ibañez, Irene Laura; Duran, Hebe Alicia; Soria, Ramiro Gaston; Gottifredi, Vanesa; et al.; Suppression of cancer growth by non-viral gene therapy based on a novel reactive oxygen species-responsive promoter; Cell Press; Molecular Therapy (print); 17; 8; 8-2009; 1355-1364
1525-0016
CONICET Digital
CONICET
url http://hdl.handle.net/11336/25652
identifier_str_mv Policastro, Lucia Laura; Ibañez, Irene Laura; Duran, Hebe Alicia; Soria, Ramiro Gaston; Gottifredi, Vanesa; et al.; Suppression of cancer growth by non-viral gene therapy based on a novel reactive oxygen species-responsive promoter; Cell Press; Molecular Therapy (print); 17; 8; 8-2009; 1355-1364
1525-0016
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(16)31856-1
info:eu-repo/semantics/altIdentifier/doi/10.1038/mt.2009.103
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
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
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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