Action of Hexachlorobenzene on tumor growth and metastasis in different experimental models

Autores
Pontillo, Carolina Andrea; Rojas, Paola Andrea; Chiappini, Florencia Ana; Sequeira, Gonzalo Ricardo; Cocca, Claudia Marcela; Crocci, Máximo; Colombo, Lucas Luis; Lanari, Claudia Lee Malvina; Kleiman de Pisarev, Diana; Randi, Andrea Silvana
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hexachlorobenzene (HCB) is a widespread organochlorine pesticide, considered a possible human carcinogen. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). We have found that HCB activates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways and cell migration, in an AhR-dependent manner in MDA-MB-231 breast cancer cells. The aim of this study was to investigate in vitro the effect of HCB (0.005, 0.05, 0.5, 5μM) on cell invasion and metalloproteases (MMPs) 2 and 9 activation in MDA-MB-231 cells. Furthermore, we examined in vivo the effect of HCB (0.3, 3, 30mg/kg b.w.) on tumor growth, MMP2 and MMP9 expression, and metastasis using MDA-MB-231 xenografts and two syngeneic mouse breast cancer models (spontaneous metastasis using C4-HI and lung experimental metastasis using LM3). Our results show that HCB (5μM) enhances MMP2 expression, as well as cell invasion, through AhR, c-Src/HER1 pathway and MMPs. Moreover, HCB increases MMP9 expression, secretion and activity through a HER1 and AhR-dependent mechanism, in MDA-MB-231 cells. HCB (0.3 and 3mg/kg b.w.) enhances subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. In vivo, using MDA-MB-231 model, the pesticide (0.3, 3 and 30mg/kg b.w.) activated c-Src, HER1, STAT5b, and ERK1/2 signaling pathways and increased MMP2 and MMP9 protein levels. Furthermore, we observed that HCB stimulated lung metastasis regardless the tumor hormone-receptor status. Our findings suggest that HCB may be a risk factor for human breast cancer progression.
Fil: Pontillo, Carolina Andrea. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Chiappini, Florencia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas . Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Sequeira, Gonzalo Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Cocca, Claudia Marcela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Físico Matemática; Argentina
Fil: Crocci, Máximo. Instituto de Inmunooncología Crescenti; Argentina
Fil: Colombo, Lucas Luis. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina
Fil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Kleiman de Pisarev, Diana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Randi, Andrea Silvana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Materia
Hexachlorobenzene
Mda-Mb-231
Cell Invasion;
Ahr
Mmps
Metastasis.
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:11336/1816
Acceder
id CONICETDig_fd6de40d86e925ce03f78d830a094103
oai_identifier_str oai:ri.conicet.gov.ar:11336/1816
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Action of Hexachlorobenzene on tumor growth and metastasis in different experimental modelsPontillo, Carolina AndreaRojas, Paola AndreaChiappini, Florencia AnaSequeira, Gonzalo RicardoCocca, Claudia MarcelaCrocci, MáximoColombo, Lucas LuisLanari, Claudia Lee MalvinaKleiman de Pisarev, DianaRandi, Andrea SilvanaHexachlorobenzeneMda-Mb-231Cell Invasion;AhrMmpsMetastasis.https://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Hexachlorobenzene (HCB) is a widespread organochlorine pesticide, considered a possible human carcinogen. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). We have found that HCB activates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways and cell migration, in an AhR-dependent manner in MDA-MB-231 breast cancer cells. The aim of this study was to investigate in vitro the effect of HCB (0.005, 0.05, 0.5, 5μM) on cell invasion and metalloproteases (MMPs) 2 and 9 activation in MDA-MB-231 cells. Furthermore, we examined in vivo the effect of HCB (0.3, 3, 30mg/kg b.w.) on tumor growth, MMP2 and MMP9 expression, and metastasis using MDA-MB-231 xenografts and two syngeneic mouse breast cancer models (spontaneous metastasis using C4-HI and lung experimental metastasis using LM3). Our results show that HCB (5μM) enhances MMP2 expression, as well as cell invasion, through AhR, c-Src/HER1 pathway and MMPs. Moreover, HCB increases MMP9 expression, secretion and activity through a HER1 and AhR-dependent mechanism, in MDA-MB-231 cells. HCB (0.3 and 3mg/kg b.w.) enhances subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. In vivo, using MDA-MB-231 model, the pesticide (0.3, 3 and 30mg/kg b.w.) activated c-Src, HER1, STAT5b, and ERK1/2 signaling pathways and increased MMP2 and MMP9 protein levels. Furthermore, we observed that HCB stimulated lung metastasis regardless the tumor hormone-receptor status. Our findings suggest that HCB may be a risk factor for human breast cancer progression.Fil: Pontillo, Carolina Andrea. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Chiappini, Florencia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas . Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Sequeira, Gonzalo Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Cocca, Claudia Marcela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Físico Matemática; ArgentinaFil: Crocci, Máximo. Instituto de Inmunooncología Crescenti; ArgentinaFil: Colombo, Lucas Luis. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; ArgentinaFil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Kleiman de Pisarev, Diana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Randi, Andrea Silvana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaElsevier2013-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/1816Pontillo, Carolina Andrea; Rojas, Paola Andrea; Chiappini, Florencia Ana; Sequeira, Gonzalo Ricardo; Cocca, Claudia Marcela; et al.; Action of Hexachlorobenzene on tumor growth and metastasis in different experimental models; Elsevier; Toxicology and Applied Pharmacology; 268; 3; 5-2013; 331-3420041-008Xenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0041008X1300077Xinfo:eu-repo/semantics/altIdentifier/doi/doi:10.1016/j.taap.2013.02.007info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:38:45Zoai:ri.conicet.gov.ar:11336/1816instacron: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 09:38:46.224CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Action of Hexachlorobenzene on tumor growth and metastasis in different experimental models
title Action of Hexachlorobenzene on tumor growth and metastasis in different experimental models
spellingShingle Action of Hexachlorobenzene on tumor growth and metastasis in different experimental models
Pontillo, Carolina Andrea
Hexachlorobenzene
Mda-Mb-231
Cell Invasion;
Ahr
Mmps
Metastasis.
title_short Action of Hexachlorobenzene on tumor growth and metastasis in different experimental models
title_full Action of Hexachlorobenzene on tumor growth and metastasis in different experimental models
title_fullStr Action of Hexachlorobenzene on tumor growth and metastasis in different experimental models
title_full_unstemmed Action of Hexachlorobenzene on tumor growth and metastasis in different experimental models
title_sort Action of Hexachlorobenzene on tumor growth and metastasis in different experimental models
dc.creator.none.fl_str_mv Pontillo, Carolina Andrea
Rojas, Paola Andrea
Chiappini, Florencia Ana
Sequeira, Gonzalo Ricardo
Cocca, Claudia Marcela
Crocci, Máximo
Colombo, Lucas Luis
Lanari, Claudia Lee Malvina
Kleiman de Pisarev, Diana
Randi, Andrea Silvana
author Pontillo, Carolina Andrea
author_facet Pontillo, Carolina Andrea
Rojas, Paola Andrea
Chiappini, Florencia Ana
Sequeira, Gonzalo Ricardo
Cocca, Claudia Marcela
Crocci, Máximo
Colombo, Lucas Luis
Lanari, Claudia Lee Malvina
Kleiman de Pisarev, Diana
Randi, Andrea Silvana
author_role author
author2 Rojas, Paola Andrea
Chiappini, Florencia Ana
Sequeira, Gonzalo Ricardo
Cocca, Claudia Marcela
Crocci, Máximo
Colombo, Lucas Luis
Lanari, Claudia Lee Malvina
Kleiman de Pisarev, Diana
Randi, Andrea Silvana
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hexachlorobenzene
Mda-Mb-231
Cell Invasion;
Ahr
Mmps
Metastasis.
topic Hexachlorobenzene
Mda-Mb-231
Cell Invasion;
Ahr
Mmps
Metastasis.
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Hexachlorobenzene (HCB) is a widespread organochlorine pesticide, considered a possible human carcinogen. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). We have found that HCB activates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways and cell migration, in an AhR-dependent manner in MDA-MB-231 breast cancer cells. The aim of this study was to investigate in vitro the effect of HCB (0.005, 0.05, 0.5, 5μM) on cell invasion and metalloproteases (MMPs) 2 and 9 activation in MDA-MB-231 cells. Furthermore, we examined in vivo the effect of HCB (0.3, 3, 30mg/kg b.w.) on tumor growth, MMP2 and MMP9 expression, and metastasis using MDA-MB-231 xenografts and two syngeneic mouse breast cancer models (spontaneous metastasis using C4-HI and lung experimental metastasis using LM3). Our results show that HCB (5μM) enhances MMP2 expression, as well as cell invasion, through AhR, c-Src/HER1 pathway and MMPs. Moreover, HCB increases MMP9 expression, secretion and activity through a HER1 and AhR-dependent mechanism, in MDA-MB-231 cells. HCB (0.3 and 3mg/kg b.w.) enhances subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. In vivo, using MDA-MB-231 model, the pesticide (0.3, 3 and 30mg/kg b.w.) activated c-Src, HER1, STAT5b, and ERK1/2 signaling pathways and increased MMP2 and MMP9 protein levels. Furthermore, we observed that HCB stimulated lung metastasis regardless the tumor hormone-receptor status. Our findings suggest that HCB may be a risk factor for human breast cancer progression.
Fil: Pontillo, Carolina Andrea. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Chiappini, Florencia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas . Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Sequeira, Gonzalo Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Cocca, Claudia Marcela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Físico Matemática; Argentina
Fil: Crocci, Máximo. Instituto de Inmunooncología Crescenti; Argentina
Fil: Colombo, Lucas Luis. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina
Fil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Kleiman de Pisarev, Diana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Randi, Andrea Silvana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
description Hexachlorobenzene (HCB) is a widespread organochlorine pesticide, considered a possible human carcinogen. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). We have found that HCB activates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways and cell migration, in an AhR-dependent manner in MDA-MB-231 breast cancer cells. The aim of this study was to investigate in vitro the effect of HCB (0.005, 0.05, 0.5, 5μM) on cell invasion and metalloproteases (MMPs) 2 and 9 activation in MDA-MB-231 cells. Furthermore, we examined in vivo the effect of HCB (0.3, 3, 30mg/kg b.w.) on tumor growth, MMP2 and MMP9 expression, and metastasis using MDA-MB-231 xenografts and two syngeneic mouse breast cancer models (spontaneous metastasis using C4-HI and lung experimental metastasis using LM3). Our results show that HCB (5μM) enhances MMP2 expression, as well as cell invasion, through AhR, c-Src/HER1 pathway and MMPs. Moreover, HCB increases MMP9 expression, secretion and activity through a HER1 and AhR-dependent mechanism, in MDA-MB-231 cells. HCB (0.3 and 3mg/kg b.w.) enhances subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. In vivo, using MDA-MB-231 model, the pesticide (0.3, 3 and 30mg/kg b.w.) activated c-Src, HER1, STAT5b, and ERK1/2 signaling pathways and increased MMP2 and MMP9 protein levels. Furthermore, we observed that HCB stimulated lung metastasis regardless the tumor hormone-receptor status. Our findings suggest that HCB may be a risk factor for human breast cancer progression.
publishDate 2013
dc.date.none.fl_str_mv 2013-05
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/11336/1816
Pontillo, Carolina Andrea; Rojas, Paola Andrea; Chiappini, Florencia Ana; Sequeira, Gonzalo Ricardo; Cocca, Claudia Marcela; et al.; Action of Hexachlorobenzene on tumor growth and metastasis in different experimental models; Elsevier; Toxicology and Applied Pharmacology; 268; 3; 5-2013; 331-342
0041-008X
url http://hdl.handle.net/11336/1816
identifier_str_mv Pontillo, Carolina Andrea; Rojas, Paola Andrea; Chiappini, Florencia Ana; Sequeira, Gonzalo Ricardo; Cocca, Claudia Marcela; et al.; Action of Hexachlorobenzene on tumor growth and metastasis in different experimental models; Elsevier; Toxicology and Applied Pharmacology; 268; 3; 5-2013; 331-342
0041-008X
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0041008X1300077X
info:eu-repo/semantics/altIdentifier/doi/doi:10.1016/j.taap.2013.02.007
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 Elsevier
publisher.none.fl_str_mv Elsevier
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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