Interferon-Β lipofection II: Mechanisms involved in cell death and bystander effect induced by cationic lipid-mediated interferon-Β gene transfer to human tumor cells

Autores
Villaverde, Marcela Solange; Gil Cardeza, Maria Lourdes; Glikin, Gerardo Claudio; Finocchiaro, Liliana Maria Elena
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We evaluated the cytotoxic effects (apoptosis, necrosis and early senescence) of human interferon-B (hIFNB) gene lipofection. The cytotoxicity of hIFNB gene lipofection resulted equivalent to that of the corresponding addition of the recombinant protein (rhIFNB) on human tumor cell lines derived from Ewing´s sarcoma (EW7 and COH) and colon (HT-29) carcinomas. However, it was stronger than rhIFNB on melanoma (M8) and breast adenocarcinoma (MCF7). To reveal the mechanisms involved in these differences, we compared the effects of hIFNB gene and rhIFNB protein on EW7 and M8 (sensitive and resistant to rhIFNB protein, respectively). Lipofection with hIFNB gene caused a mitochondrial potential decrease simultaneous with an increase of oxidative stress in both cell lines. However, rhIFNB protein displayed the same pattern of response only in EW7-sensitive cell line. The great bystander effect of the hIFNB gene lipofection, involving the production of reactive oxygen species, would be among the main causes of its success. In EW7, this effect killed >60% of EW7 cell population, even though only 1% of cells were expressing the transgene. As hIFNB gene was effective even in the rhIFNB protein-resistant M8 cell line and in a way not limited by low lipofection efficiency, these results strongly support the clinical potential of this approach.
Fil: Villaverde, Marcela Solange. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Gil Cardeza, Maria Lourdes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Glikin, Gerardo Claudio. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Finocchiaro, Liliana Maria Elena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Materia
APOPTOSIS
EWING'S SARCOMA
INTERFERON-B
LIPOFECTION
MELANOMA
REACTIVE OXYGEN SPECIES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/162317
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/162317
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Interferon-Β lipofection II: Mechanisms involved in cell death and bystander effect induced by cationic lipid-mediated interferon-Β gene transfer to human tumor cellsVillaverde, Marcela SolangeGil Cardeza, Maria LourdesGlikin, Gerardo ClaudioFinocchiaro, Liliana Maria ElenaAPOPTOSISEWING'S SARCOMAINTERFERON-BLIPOFECTIONMELANOMAREACTIVE OXYGEN SPECIEShttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3We evaluated the cytotoxic effects (apoptosis, necrosis and early senescence) of human interferon-B (hIFNB) gene lipofection. The cytotoxicity of hIFNB gene lipofection resulted equivalent to that of the corresponding addition of the recombinant protein (rhIFNB) on human tumor cell lines derived from Ewing´s sarcoma (EW7 and COH) and colon (HT-29) carcinomas. However, it was stronger than rhIFNB on melanoma (M8) and breast adenocarcinoma (MCF7). To reveal the mechanisms involved in these differences, we compared the effects of hIFNB gene and rhIFNB protein on EW7 and M8 (sensitive and resistant to rhIFNB protein, respectively). Lipofection with hIFNB gene caused a mitochondrial potential decrease simultaneous with an increase of oxidative stress in both cell lines. However, rhIFNB protein displayed the same pattern of response only in EW7-sensitive cell line. The great bystander effect of the hIFNB gene lipofection, involving the production of reactive oxygen species, would be among the main causes of its success. In EW7, this effect killed >60% of EW7 cell population, even though only 1% of cells were expressing the transgene. As hIFNB gene was effective even in the rhIFNB protein-resistant M8 cell line and in a way not limited by low lipofection efficiency, these results strongly support the clinical potential of this approach.Fil: Villaverde, Marcela Solange. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Gil Cardeza, Maria Lourdes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Glikin, Gerardo Claudio. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Finocchiaro, Liliana Maria Elena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaNature Publishing Group2012-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/162317Villaverde, Marcela Solange; Gil Cardeza, Maria Lourdes; Glikin, Gerardo Claudio; Finocchiaro, Liliana Maria Elena; Interferon-Β lipofection II: Mechanisms involved in cell death and bystander effect induced by cationic lipid-mediated interferon-Β gene transfer to human tumor cells; Nature Publishing Group; Cancer Gene Therapy; 19; 6; 6-2012; 420-4300929-1903CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/cgt201219info:eu-repo/semantics/altIdentifier/doi/10.1038/cgt.2012.19info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:46:36Zoai:ri.conicet.gov.ar:11336/162317instacron: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:34982025-09-03 09:46:36.775CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Interferon-Β lipofection II: Mechanisms involved in cell death and bystander effect induced by cationic lipid-mediated interferon-Β gene transfer to human tumor cells
title Interferon-Β lipofection II: Mechanisms involved in cell death and bystander effect induced by cationic lipid-mediated interferon-Β gene transfer to human tumor cells
spellingShingle Interferon-Β lipofection II: Mechanisms involved in cell death and bystander effect induced by cationic lipid-mediated interferon-Β gene transfer to human tumor cells
Villaverde, Marcela Solange
APOPTOSIS
EWING'S SARCOMA
INTERFERON-B
LIPOFECTION
MELANOMA
REACTIVE OXYGEN SPECIES
title_short Interferon-Β lipofection II: Mechanisms involved in cell death and bystander effect induced by cationic lipid-mediated interferon-Β gene transfer to human tumor cells
title_full Interferon-Β lipofection II: Mechanisms involved in cell death and bystander effect induced by cationic lipid-mediated interferon-Β gene transfer to human tumor cells
title_fullStr Interferon-Β lipofection II: Mechanisms involved in cell death and bystander effect induced by cationic lipid-mediated interferon-Β gene transfer to human tumor cells
title_full_unstemmed Interferon-Β lipofection II: Mechanisms involved in cell death and bystander effect induced by cationic lipid-mediated interferon-Β gene transfer to human tumor cells
title_sort Interferon-Β lipofection II: Mechanisms involved in cell death and bystander effect induced by cationic lipid-mediated interferon-Β gene transfer to human tumor cells
dc.creator.none.fl_str_mv Villaverde, Marcela Solange
Gil Cardeza, Maria Lourdes
Glikin, Gerardo Claudio
Finocchiaro, Liliana Maria Elena
author Villaverde, Marcela Solange
author_facet Villaverde, Marcela Solange
Gil Cardeza, Maria Lourdes
Glikin, Gerardo Claudio
Finocchiaro, Liliana Maria Elena
author_role author
author2 Gil Cardeza, Maria Lourdes
Glikin, Gerardo Claudio
Finocchiaro, Liliana Maria Elena
author2_role author
author
author
dc.subject.none.fl_str_mv APOPTOSIS
EWING'S SARCOMA
INTERFERON-B
LIPOFECTION
MELANOMA
REACTIVE OXYGEN SPECIES
topic APOPTOSIS
EWING'S SARCOMA
INTERFERON-B
LIPOFECTION
MELANOMA
REACTIVE OXYGEN SPECIES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv We evaluated the cytotoxic effects (apoptosis, necrosis and early senescence) of human interferon-B (hIFNB) gene lipofection. The cytotoxicity of hIFNB gene lipofection resulted equivalent to that of the corresponding addition of the recombinant protein (rhIFNB) on human tumor cell lines derived from Ewing´s sarcoma (EW7 and COH) and colon (HT-29) carcinomas. However, it was stronger than rhIFNB on melanoma (M8) and breast adenocarcinoma (MCF7). To reveal the mechanisms involved in these differences, we compared the effects of hIFNB gene and rhIFNB protein on EW7 and M8 (sensitive and resistant to rhIFNB protein, respectively). Lipofection with hIFNB gene caused a mitochondrial potential decrease simultaneous with an increase of oxidative stress in both cell lines. However, rhIFNB protein displayed the same pattern of response only in EW7-sensitive cell line. The great bystander effect of the hIFNB gene lipofection, involving the production of reactive oxygen species, would be among the main causes of its success. In EW7, this effect killed >60% of EW7 cell population, even though only 1% of cells were expressing the transgene. As hIFNB gene was effective even in the rhIFNB protein-resistant M8 cell line and in a way not limited by low lipofection efficiency, these results strongly support the clinical potential of this approach.
Fil: Villaverde, Marcela Solange. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Gil Cardeza, Maria Lourdes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Glikin, Gerardo Claudio. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Finocchiaro, Liliana Maria Elena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
description We evaluated the cytotoxic effects (apoptosis, necrosis and early senescence) of human interferon-B (hIFNB) gene lipofection. The cytotoxicity of hIFNB gene lipofection resulted equivalent to that of the corresponding addition of the recombinant protein (rhIFNB) on human tumor cell lines derived from Ewing´s sarcoma (EW7 and COH) and colon (HT-29) carcinomas. However, it was stronger than rhIFNB on melanoma (M8) and breast adenocarcinoma (MCF7). To reveal the mechanisms involved in these differences, we compared the effects of hIFNB gene and rhIFNB protein on EW7 and M8 (sensitive and resistant to rhIFNB protein, respectively). Lipofection with hIFNB gene caused a mitochondrial potential decrease simultaneous with an increase of oxidative stress in both cell lines. However, rhIFNB protein displayed the same pattern of response only in EW7-sensitive cell line. The great bystander effect of the hIFNB gene lipofection, involving the production of reactive oxygen species, would be among the main causes of its success. In EW7, this effect killed >60% of EW7 cell population, even though only 1% of cells were expressing the transgene. As hIFNB gene was effective even in the rhIFNB protein-resistant M8 cell line and in a way not limited by low lipofection efficiency, these results strongly support the clinical potential of this approach.
publishDate 2012
dc.date.none.fl_str_mv 2012-06
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/11336/162317
Villaverde, Marcela Solange; Gil Cardeza, Maria Lourdes; Glikin, Gerardo Claudio; Finocchiaro, Liliana Maria Elena; Interferon-Β lipofection II: Mechanisms involved in cell death and bystander effect induced by cationic lipid-mediated interferon-Β gene transfer to human tumor cells; Nature Publishing Group; Cancer Gene Therapy; 19; 6; 6-2012; 420-430
0929-1903
CONICET Digital
CONICET
url http://hdl.handle.net/11336/162317
identifier_str_mv Villaverde, Marcela Solange; Gil Cardeza, Maria Lourdes; Glikin, Gerardo Claudio; Finocchiaro, Liliana Maria Elena; Interferon-Β lipofection II: Mechanisms involved in cell death and bystander effect induced by cationic lipid-mediated interferon-Β gene transfer to human tumor cells; Nature Publishing Group; Cancer Gene Therapy; 19; 6; 6-2012; 420-430
0929-1903
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://www.nature.com/articles/cgt201219
info:eu-repo/semantics/altIdentifier/doi/10.1038/cgt.2012.19
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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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