Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology

Autores
Mateu-Jimenez, Mercè; Fermoselle, Clara; Rojo, Federico; Mateu, Javier; Peña, Raúl; Urtreger, Alejandro Jorge; Diament, Miriam; Bal, Elisa Dora; Pijuan, Lara; Herreros, Antonio; Barreiro, Esther
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Lung cancer (LC) remains the leading cause of cancer mortality worldwide, and non-small cell LC (NSCLC) represents 80% of all LC. Oxidative stress and inflammation, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-KB, and mitogen activated protein kinases (MAPK) participate in LC pathophysiology. Currently available treatment for LC is limited and in vivo models are lacking. We hypothesized that antioxidants and NF-KB, MAPK, and proteasome inhibitors may exert an antitumoral response through attenuation of several key biological mechanisms that promote tumorigenesis and cancer cell growth. Body and tumor weights, oxidative stress, antioxidants, inflammation, NF-KB p65 expression, fibulins, apoptosis, autophagy, tumor and stroma histology were evaluated in the subcutaneous tumor of LC (LP07) adenocarcinoma) BALB/c mice, with and without concomitant treatment with NF-KB (sulfasalazine), MEK (U0126), and proteasome (bortezomib) inhibitors, and N-acetyl cysteine (NAC). Compared to LC control mice, in subcutaneous tumors, the four pharmacological agents reduced oxidative stress markers and tumor proliferation (ki-67). Inflammation and NF-KB p65 expression were attenuated by NF-KB and MAPK inhibitors, and the latter also enhanced apoptotic markers. Catalase was induced by the three inhibitors, while bortezomib also promoted superoxide dismutase expression. NF-KB and MEK inhibitors significantly reduced tumor burden through several biological mechanisms that favored tumor degradation and attenuated tumor proliferation. These two pharmacological agents may enhance the anti-tumor activity of selectively targeted therapeutic strategies for LC. Proteasomal inhibition using bortezomib rather promotes tumor degradation, while treatment with antioxidants cannot be recommended. This experimental model supports the use of adjuvant drugs for the improvement of LC treatment.
Fil: Mateu-Jimenez, Mercè. Barcelona Biomedical Research Park; España
Fil: Fermoselle, Clara. Barcelona Biomedical Research Park; España
Fil: Rojo, Federico. Fundación Jiménez Díaz; España
Fil: Mateu, Javier. Hospital del Mar; España
Fil: Peña, Raúl. Hospital del Mar; España
Fil: Urtreger, Alejandro Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Diament, Miriam. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Bal, Elisa Dora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Pijuan, Lara. Hospital del Mar; España
Fil: Herreros, Antonio. Hospital del Mar; España
Fil: Barreiro, Esther. Barcelona Biomedical Research Park; España
Materia
Non-Small Cell Lung Cancer
Mapk
Nf-Kb
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:11336/47973
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/47973
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor BiologyMateu-Jimenez, MercèFermoselle, ClaraRojo, FedericoMateu, JavierPeña, RaúlUrtreger, Alejandro JorgeDiament, MiriamBal, Elisa DoraPijuan, LaraHerreros, AntonioBarreiro, EstherNon-Small Cell Lung CancerMapkNf-Kbhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Lung cancer (LC) remains the leading cause of cancer mortality worldwide, and non-small cell LC (NSCLC) represents 80% of all LC. Oxidative stress and inflammation, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-KB, and mitogen activated protein kinases (MAPK) participate in LC pathophysiology. Currently available treatment for LC is limited and in vivo models are lacking. We hypothesized that antioxidants and NF-KB, MAPK, and proteasome inhibitors may exert an antitumoral response through attenuation of several key biological mechanisms that promote tumorigenesis and cancer cell growth. Body and tumor weights, oxidative stress, antioxidants, inflammation, NF-KB p65 expression, fibulins, apoptosis, autophagy, tumor and stroma histology were evaluated in the subcutaneous tumor of LC (LP07) adenocarcinoma) BALB/c mice, with and without concomitant treatment with NF-KB (sulfasalazine), MEK (U0126), and proteasome (bortezomib) inhibitors, and N-acetyl cysteine (NAC). Compared to LC control mice, in subcutaneous tumors, the four pharmacological agents reduced oxidative stress markers and tumor proliferation (ki-67). Inflammation and NF-KB p65 expression were attenuated by NF-KB and MAPK inhibitors, and the latter also enhanced apoptotic markers. Catalase was induced by the three inhibitors, while bortezomib also promoted superoxide dismutase expression. NF-KB and MEK inhibitors significantly reduced tumor burden through several biological mechanisms that favored tumor degradation and attenuated tumor proliferation. These two pharmacological agents may enhance the anti-tumor activity of selectively targeted therapeutic strategies for LC. Proteasomal inhibition using bortezomib rather promotes tumor degradation, while treatment with antioxidants cannot be recommended. This experimental model supports the use of adjuvant drugs for the improvement of LC treatment.Fil: Mateu-Jimenez, Mercè. Barcelona Biomedical Research Park; EspañaFil: Fermoselle, Clara. Barcelona Biomedical Research Park; EspañaFil: Rojo, Federico. Fundación Jiménez Díaz; EspañaFil: Mateu, Javier. Hospital del Mar; EspañaFil: Peña, Raúl. Hospital del Mar; EspañaFil: Urtreger, Alejandro Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Diament, Miriam. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Bal, Elisa Dora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Pijuan, Lara. Hospital del Mar; EspañaFil: Herreros, Antonio. Hospital del Mar; EspañaFil: Barreiro, Esther. Barcelona Biomedical Research Park; EspañaBentham Science Publishers2016-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/47973Mateu-Jimenez, Mercè; Fermoselle, Clara; Rojo, Federico; Mateu, Javier; Peña, Raúl; et al.; Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology; Bentham Science Publishers; Current Pharmaceutical Design; 22; 34; 11-2016; 5300-53101381-6128CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.2174/1381612822666160623065523info:eu-repo/semantics/altIdentifier/url/http://www.eurekaselect.com/143505/articleinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:36:57Zoai:ri.conicet.gov.ar:11336/47973instacron: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 09:36:57.343CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology
title Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology
spellingShingle Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology
Mateu-Jimenez, Mercè
Non-Small Cell Lung Cancer
Mapk
Nf-Kb
title_short Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology
title_full Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology
title_fullStr Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology
title_full_unstemmed Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology
title_sort Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology
dc.creator.none.fl_str_mv Mateu-Jimenez, Mercè
Fermoselle, Clara
Rojo, Federico
Mateu, Javier
Peña, Raúl
Urtreger, Alejandro Jorge
Diament, Miriam
Bal, Elisa Dora
Pijuan, Lara
Herreros, Antonio
Barreiro, Esther
author Mateu-Jimenez, Mercè
author_facet Mateu-Jimenez, Mercè
Fermoselle, Clara
Rojo, Federico
Mateu, Javier
Peña, Raúl
Urtreger, Alejandro Jorge
Diament, Miriam
Bal, Elisa Dora
Pijuan, Lara
Herreros, Antonio
Barreiro, Esther
author_role author
author2 Fermoselle, Clara
Rojo, Federico
Mateu, Javier
Peña, Raúl
Urtreger, Alejandro Jorge
Diament, Miriam
Bal, Elisa Dora
Pijuan, Lara
Herreros, Antonio
Barreiro, Esther
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Non-Small Cell Lung Cancer
Mapk
Nf-Kb
topic Non-Small Cell Lung Cancer
Mapk
Nf-Kb
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Lung cancer (LC) remains the leading cause of cancer mortality worldwide, and non-small cell LC (NSCLC) represents 80% of all LC. Oxidative stress and inflammation, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-KB, and mitogen activated protein kinases (MAPK) participate in LC pathophysiology. Currently available treatment for LC is limited and in vivo models are lacking. We hypothesized that antioxidants and NF-KB, MAPK, and proteasome inhibitors may exert an antitumoral response through attenuation of several key biological mechanisms that promote tumorigenesis and cancer cell growth. Body and tumor weights, oxidative stress, antioxidants, inflammation, NF-KB p65 expression, fibulins, apoptosis, autophagy, tumor and stroma histology were evaluated in the subcutaneous tumor of LC (LP07) adenocarcinoma) BALB/c mice, with and without concomitant treatment with NF-KB (sulfasalazine), MEK (U0126), and proteasome (bortezomib) inhibitors, and N-acetyl cysteine (NAC). Compared to LC control mice, in subcutaneous tumors, the four pharmacological agents reduced oxidative stress markers and tumor proliferation (ki-67). Inflammation and NF-KB p65 expression were attenuated by NF-KB and MAPK inhibitors, and the latter also enhanced apoptotic markers. Catalase was induced by the three inhibitors, while bortezomib also promoted superoxide dismutase expression. NF-KB and MEK inhibitors significantly reduced tumor burden through several biological mechanisms that favored tumor degradation and attenuated tumor proliferation. These two pharmacological agents may enhance the anti-tumor activity of selectively targeted therapeutic strategies for LC. Proteasomal inhibition using bortezomib rather promotes tumor degradation, while treatment with antioxidants cannot be recommended. This experimental model supports the use of adjuvant drugs for the improvement of LC treatment.
Fil: Mateu-Jimenez, Mercè. Barcelona Biomedical Research Park; España
Fil: Fermoselle, Clara. Barcelona Biomedical Research Park; España
Fil: Rojo, Federico. Fundación Jiménez Díaz; España
Fil: Mateu, Javier. Hospital del Mar; España
Fil: Peña, Raúl. Hospital del Mar; España
Fil: Urtreger, Alejandro Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Diament, Miriam. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Bal, Elisa Dora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Pijuan, Lara. Hospital del Mar; España
Fil: Herreros, Antonio. Hospital del Mar; España
Fil: Barreiro, Esther. Barcelona Biomedical Research Park; España
description Lung cancer (LC) remains the leading cause of cancer mortality worldwide, and non-small cell LC (NSCLC) represents 80% of all LC. Oxidative stress and inflammation, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-KB, and mitogen activated protein kinases (MAPK) participate in LC pathophysiology. Currently available treatment for LC is limited and in vivo models are lacking. We hypothesized that antioxidants and NF-KB, MAPK, and proteasome inhibitors may exert an antitumoral response through attenuation of several key biological mechanisms that promote tumorigenesis and cancer cell growth. Body and tumor weights, oxidative stress, antioxidants, inflammation, NF-KB p65 expression, fibulins, apoptosis, autophagy, tumor and stroma histology were evaluated in the subcutaneous tumor of LC (LP07) adenocarcinoma) BALB/c mice, with and without concomitant treatment with NF-KB (sulfasalazine), MEK (U0126), and proteasome (bortezomib) inhibitors, and N-acetyl cysteine (NAC). Compared to LC control mice, in subcutaneous tumors, the four pharmacological agents reduced oxidative stress markers and tumor proliferation (ki-67). Inflammation and NF-KB p65 expression were attenuated by NF-KB and MAPK inhibitors, and the latter also enhanced apoptotic markers. Catalase was induced by the three inhibitors, while bortezomib also promoted superoxide dismutase expression. NF-KB and MEK inhibitors significantly reduced tumor burden through several biological mechanisms that favored tumor degradation and attenuated tumor proliferation. These two pharmacological agents may enhance the anti-tumor activity of selectively targeted therapeutic strategies for LC. Proteasomal inhibition using bortezomib rather promotes tumor degradation, while treatment with antioxidants cannot be recommended. This experimental model supports the use of adjuvant drugs for the improvement of LC treatment.
publishDate 2016
dc.date.none.fl_str_mv 2016-11
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/11336/47973
Mateu-Jimenez, Mercè; Fermoselle, Clara; Rojo, Federico; Mateu, Javier; Peña, Raúl; et al.; Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology; Bentham Science Publishers; Current Pharmaceutical Design; 22; 34; 11-2016; 5300-5310
1381-6128
CONICET Digital
CONICET
url http://hdl.handle.net/11336/47973
identifier_str_mv Mateu-Jimenez, Mercè; Fermoselle, Clara; Rojo, Federico; Mateu, Javier; Peña, Raúl; et al.; Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology; Bentham Science Publishers; Current Pharmaceutical Design; 22; 34; 11-2016; 5300-5310
1381-6128
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.2174/1381612822666160623065523
info:eu-repo/semantics/altIdentifier/url/http://www.eurekaselect.com/143505/article
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 Bentham Science Publishers
publisher.none.fl_str_mv Bentham Science Publishers
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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