Chlorpyrifos subthreshold exposure induces epithelial-mesenchymal transition in breast cancer cells

Autores
Lasagna, Marianela; Hielpos, María Soledad; Ventura, Clara; Mardirosian, Mariana Noelia; Martín, G.; Miret, Noelia Victoria; Randi, Andrea Silvana; Núñez, M.; Cocca, Claudia Marcela
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chlorpyrifos (CPF) is one of the most frequently used pesticide in extensive agriculture around the world and can be incorporated by humans and animals with possible consequences on health. The effects of this pesticide on carcinogenesis are not clear and there is no consensus concerning the risks of this compound. In previous work, we demonstrated that CPF induces proliferation of breast cancer cells both in vivo and in vitro. In this work we investigate whether CPF promotes the epithelial-mesenchymal transition (EMT) in breast cancer cells. Herein, we demonstrate that 50 μM CFP induces invasion in MCF-7 and MDA-MB-231 cells. In addition, 0.05 and 50 μM CPF increases migration in both cell lines. In MCF-7 cells, 0.05 and 50 μM CPF increase the metalloprotease MMP2 expression and decrease E-Cadherin and β-Catenin expression diminishing their membrane location. Furthermore, 50 μM CPF induces Vimentin expression and Slug nuclear translocation in MCF-7 cells. 0.05 and 50 μM CPF increase MMP2 gelatinolytic activity and expression, decrease β-Catenin expression and increase Vimentin expression in MDA-MB-231 cells. Inhibition of the oncoprotein c-Src reverses all the effects induced by CPF in MDA-MB-231 but not in MCF-7 indicating that c-Src is a kinase with a crucial role in the cells which grow in an estrogen-independent way. In MCF-7 cells both c-Src and estrogen receptor alpha must be blocked to completly inhibit the CPF-mediated effects. Our results show for the first time that the exposure to subthreshold concentrations of CPF promotes the modulation of EMT-molecular markers and pathways. These results, together with the ubiquitous distribution of the pesticide CPF, make it of utmost importance to take measures to minimize the risk of exposure to this compound.
Fil: Lasagna, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Hielpos, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Ventura, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Mardirosian, Mariana Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Martín, G.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Miret, Noelia Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Randi, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Núñez, M.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Cocca, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Materia
BREAST CANCER
CELL SIGNALING
CHLORPYRIFOS
ENDOCRINE DISRUPTORS
ENVIRONMENTAL EXPOSURE
EPITHELIAL-MESENCHYMAL TRANSITION
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:11336/116789
Acceder
id CONICETDig_288f4a805dced6d1196e028ad05bbd8f
oai_identifier_str oai:ri.conicet.gov.ar:11336/116789
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Chlorpyrifos subthreshold exposure induces epithelial-mesenchymal transition in breast cancer cellsLasagna, MarianelaHielpos, María SoledadVentura, ClaraMardirosian, Mariana NoeliaMartín, G.Miret, Noelia VictoriaRandi, Andrea SilvanaNúñez, M.Cocca, Claudia MarcelaBREAST CANCERCELL SIGNALINGCHLORPYRIFOSENDOCRINE DISRUPTORSENVIRONMENTAL EXPOSUREEPITHELIAL-MESENCHYMAL TRANSITIONhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Chlorpyrifos (CPF) is one of the most frequently used pesticide in extensive agriculture around the world and can be incorporated by humans and animals with possible consequences on health. The effects of this pesticide on carcinogenesis are not clear and there is no consensus concerning the risks of this compound. In previous work, we demonstrated that CPF induces proliferation of breast cancer cells both in vivo and in vitro. In this work we investigate whether CPF promotes the epithelial-mesenchymal transition (EMT) in breast cancer cells. Herein, we demonstrate that 50 μM CFP induces invasion in MCF-7 and MDA-MB-231 cells. In addition, 0.05 and 50 μM CPF increases migration in both cell lines. In MCF-7 cells, 0.05 and 50 μM CPF increase the metalloprotease MMP2 expression and decrease E-Cadherin and β-Catenin expression diminishing their membrane location. Furthermore, 50 μM CPF induces Vimentin expression and Slug nuclear translocation in MCF-7 cells. 0.05 and 50 μM CPF increase MMP2 gelatinolytic activity and expression, decrease β-Catenin expression and increase Vimentin expression in MDA-MB-231 cells. Inhibition of the oncoprotein c-Src reverses all the effects induced by CPF in MDA-MB-231 but not in MCF-7 indicating that c-Src is a kinase with a crucial role in the cells which grow in an estrogen-independent way. In MCF-7 cells both c-Src and estrogen receptor alpha must be blocked to completly inhibit the CPF-mediated effects. Our results show for the first time that the exposure to subthreshold concentrations of CPF promotes the modulation of EMT-molecular markers and pathways. These results, together with the ubiquitous distribution of the pesticide CPF, make it of utmost importance to take measures to minimize the risk of exposure to this compound.Fil: Lasagna, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Hielpos, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Ventura, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Mardirosian, Mariana Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Martín, G.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Miret, Noelia Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Randi, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Núñez, M.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Cocca, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaAcademic Press Inc Elsevier Science2020-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/116789Lasagna, Marianela; Hielpos, María Soledad; Ventura, Clara; Mardirosian, Mariana Noelia; Martín, G.; et al.; Chlorpyrifos subthreshold exposure induces epithelial-mesenchymal transition in breast cancer cells; Academic Press Inc Elsevier Science; Ecotoxicology and Environmental Safety; 205; 12-2020; 1-130147-6513CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ecoenv.2020.111312info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0147651320311490?via%3Dihubinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:52:13Zoai:ri.conicet.gov.ar:11336/116789instacron: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 09:52:13.316CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Chlorpyrifos subthreshold exposure induces epithelial-mesenchymal transition in breast cancer cells
title Chlorpyrifos subthreshold exposure induces epithelial-mesenchymal transition in breast cancer cells
spellingShingle Chlorpyrifos subthreshold exposure induces epithelial-mesenchymal transition in breast cancer cells
Lasagna, Marianela
BREAST CANCER
CELL SIGNALING
CHLORPYRIFOS
ENDOCRINE DISRUPTORS
ENVIRONMENTAL EXPOSURE
EPITHELIAL-MESENCHYMAL TRANSITION
title_short Chlorpyrifos subthreshold exposure induces epithelial-mesenchymal transition in breast cancer cells
title_full Chlorpyrifos subthreshold exposure induces epithelial-mesenchymal transition in breast cancer cells
title_fullStr Chlorpyrifos subthreshold exposure induces epithelial-mesenchymal transition in breast cancer cells
title_full_unstemmed Chlorpyrifos subthreshold exposure induces epithelial-mesenchymal transition in breast cancer cells
title_sort Chlorpyrifos subthreshold exposure induces epithelial-mesenchymal transition in breast cancer cells
dc.creator.none.fl_str_mv Lasagna, Marianela
Hielpos, María Soledad
Ventura, Clara
Mardirosian, Mariana Noelia
Martín, G.
Miret, Noelia Victoria
Randi, Andrea Silvana
Núñez, M.
Cocca, Claudia Marcela
author Lasagna, Marianela
author_facet Lasagna, Marianela
Hielpos, María Soledad
Ventura, Clara
Mardirosian, Mariana Noelia
Martín, G.
Miret, Noelia Victoria
Randi, Andrea Silvana
Núñez, M.
Cocca, Claudia Marcela
author_role author
author2 Hielpos, María Soledad
Ventura, Clara
Mardirosian, Mariana Noelia
Martín, G.
Miret, Noelia Victoria
Randi, Andrea Silvana
Núñez, M.
Cocca, Claudia Marcela
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BREAST CANCER
CELL SIGNALING
CHLORPYRIFOS
ENDOCRINE DISRUPTORS
ENVIRONMENTAL EXPOSURE
EPITHELIAL-MESENCHYMAL TRANSITION
topic BREAST CANCER
CELL SIGNALING
CHLORPYRIFOS
ENDOCRINE DISRUPTORS
ENVIRONMENTAL EXPOSURE
EPITHELIAL-MESENCHYMAL TRANSITION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Chlorpyrifos (CPF) is one of the most frequently used pesticide in extensive agriculture around the world and can be incorporated by humans and animals with possible consequences on health. The effects of this pesticide on carcinogenesis are not clear and there is no consensus concerning the risks of this compound. In previous work, we demonstrated that CPF induces proliferation of breast cancer cells both in vivo and in vitro. In this work we investigate whether CPF promotes the epithelial-mesenchymal transition (EMT) in breast cancer cells. Herein, we demonstrate that 50 μM CFP induces invasion in MCF-7 and MDA-MB-231 cells. In addition, 0.05 and 50 μM CPF increases migration in both cell lines. In MCF-7 cells, 0.05 and 50 μM CPF increase the metalloprotease MMP2 expression and decrease E-Cadherin and β-Catenin expression diminishing their membrane location. Furthermore, 50 μM CPF induces Vimentin expression and Slug nuclear translocation in MCF-7 cells. 0.05 and 50 μM CPF increase MMP2 gelatinolytic activity and expression, decrease β-Catenin expression and increase Vimentin expression in MDA-MB-231 cells. Inhibition of the oncoprotein c-Src reverses all the effects induced by CPF in MDA-MB-231 but not in MCF-7 indicating that c-Src is a kinase with a crucial role in the cells which grow in an estrogen-independent way. In MCF-7 cells both c-Src and estrogen receptor alpha must be blocked to completly inhibit the CPF-mediated effects. Our results show for the first time that the exposure to subthreshold concentrations of CPF promotes the modulation of EMT-molecular markers and pathways. These results, together with the ubiquitous distribution of the pesticide CPF, make it of utmost importance to take measures to minimize the risk of exposure to this compound.
Fil: Lasagna, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Hielpos, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Ventura, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Mardirosian, Mariana Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Martín, G.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Miret, Noelia Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Randi, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Núñez, M.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Cocca, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
description Chlorpyrifos (CPF) is one of the most frequently used pesticide in extensive agriculture around the world and can be incorporated by humans and animals with possible consequences on health. The effects of this pesticide on carcinogenesis are not clear and there is no consensus concerning the risks of this compound. In previous work, we demonstrated that CPF induces proliferation of breast cancer cells both in vivo and in vitro. In this work we investigate whether CPF promotes the epithelial-mesenchymal transition (EMT) in breast cancer cells. Herein, we demonstrate that 50 μM CFP induces invasion in MCF-7 and MDA-MB-231 cells. In addition, 0.05 and 50 μM CPF increases migration in both cell lines. In MCF-7 cells, 0.05 and 50 μM CPF increase the metalloprotease MMP2 expression and decrease E-Cadherin and β-Catenin expression diminishing their membrane location. Furthermore, 50 μM CPF induces Vimentin expression and Slug nuclear translocation in MCF-7 cells. 0.05 and 50 μM CPF increase MMP2 gelatinolytic activity and expression, decrease β-Catenin expression and increase Vimentin expression in MDA-MB-231 cells. Inhibition of the oncoprotein c-Src reverses all the effects induced by CPF in MDA-MB-231 but not in MCF-7 indicating that c-Src is a kinase with a crucial role in the cells which grow in an estrogen-independent way. In MCF-7 cells both c-Src and estrogen receptor alpha must be blocked to completly inhibit the CPF-mediated effects. Our results show for the first time that the exposure to subthreshold concentrations of CPF promotes the modulation of EMT-molecular markers and pathways. These results, together with the ubiquitous distribution of the pesticide CPF, make it of utmost importance to take measures to minimize the risk of exposure to this compound.
publishDate 2020
dc.date.none.fl_str_mv 2020-12
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/11336/116789
Lasagna, Marianela; Hielpos, María Soledad; Ventura, Clara; Mardirosian, Mariana Noelia; Martín, G.; et al.; Chlorpyrifos subthreshold exposure induces epithelial-mesenchymal transition in breast cancer cells; Academic Press Inc Elsevier Science; Ecotoxicology and Environmental Safety; 205; 12-2020; 1-13
0147-6513
CONICET Digital
CONICET
url http://hdl.handle.net/11336/116789
identifier_str_mv Lasagna, Marianela; Hielpos, María Soledad; Ventura, Clara; Mardirosian, Mariana Noelia; Martín, G.; et al.; Chlorpyrifos subthreshold exposure induces epithelial-mesenchymal transition in breast cancer cells; Academic Press Inc Elsevier Science; Ecotoxicology and Environmental Safety; 205; 12-2020; 1-13
0147-6513
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.ecoenv.2020.111312
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0147651320311490?via%3Dihub
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 Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
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 13.13397

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