Pharmacological strategies in lung cancer-induced cachexia: effects on muscle proteolysis, autophagy, structure, and weakness

Autores
Chacon Cabrera, Alba; Fermoselle, Clara; Urtreger, Alejandro Jorge; Mateu Jimenez, Mercè; Diament, Miriam; Bal, Elisa Dora; Sandri, Marco; Barreiro, Eshter
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Muscle wasting and cachexia are important systemic manifestations of highly prevalent conditions including cancer. Inflammation, oxidative stress, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-kB, and mitogen activated protein kinases (MAPK) are involved in the pathophysiology of cancer cachexia. Currently available treatment is limited and data demonstrating effectiveness in in vivo models are lacking. Our objectives were to explore in respiratory and limb muscles of lung cancer (LC) cachectic mice whether proteasome, NF-kB, and MAPK inhibitors improve muscle mass and function loss through several molecular mechanisms. Body and muscle weights, limb muscle force, protein degradation and the ubiquitin-proteasome system, signaling pathways, oxidative stress and inflammation, autophagy, contractile and functional proteins, myostatin and myogenin, and muscle structure were evaluated in the diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing cachectic mice (BALB/c), with and without concomitant treatment with NF-kB (sulfasalazine), MAPK (U0126), and proteasome (bortezomib) inhibitors. Compared to control animals, in both respiratory and limb muscles of LC cachectic mice: muscle proteolysis, ubiquitinated proteins, autophagy, myostatin, protein oxidation, FoxO-1, NF-kB and MAPK signaling pathways, and muscle abnormalities were increased, while myosin, creatine kinase, myogenin, and slow- and fast-twitch muscle fiber size were decreased. Pharmacological inhibition of NF-kB and MAPK, but not the proteasome system, induced in cancer-induced cachectic animals, a substantial restoration of muscle mass and force through a decrease in muscle protein oxidation and catabolism, myostatin, and autophagy, together with a greater content of myogenin, and contractile and functional proteins. These findings may offer new therapeutic strategies in cancer-induced cachexia.
Fil: Chacon Cabrera, Alba. Universitat Pompeu Fabra; España. Universidad Carlos III de Madrid. Instituto de Salud; España
Fil: Fermoselle, Clara. Universitat Pompeu Fabra; España. Universidad Carlos III de Madrid. Instituto de Salud; España
Fil: Urtreger, Alejandro Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Mateu Jimenez, Mercè. Universidad Carlos III de Madrid. Instituto de Salud; España. Universitat Pompeu Fabra; España
Fil: Diament, Miriam. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina
Fil: Bal, Elisa Dora. 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: Sandri, Marco. Università di Padova; Italia
Fil: Barreiro, Eshter. Universitat Pompeu Fabra; España. Universidad Carlos III de Madrid. Instituto de Salud; España
Materia
Lung Cancer
Cachexia
Pharmacology
Autophagy
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:11336/30354
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/30354
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Pharmacological strategies in lung cancer-induced cachexia: effects on muscle proteolysis, autophagy, structure, and weaknessChacon Cabrera, AlbaFermoselle, ClaraUrtreger, Alejandro JorgeMateu Jimenez, MercèDiament, MiriamBal, Elisa DoraSandri, MarcoBarreiro, EshterLung CancerCachexiaPharmacologyAutophagyhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Muscle wasting and cachexia are important systemic manifestations of highly prevalent conditions including cancer. Inflammation, oxidative stress, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-kB, and mitogen activated protein kinases (MAPK) are involved in the pathophysiology of cancer cachexia. Currently available treatment is limited and data demonstrating effectiveness in in vivo models are lacking. Our objectives were to explore in respiratory and limb muscles of lung cancer (LC) cachectic mice whether proteasome, NF-kB, and MAPK inhibitors improve muscle mass and function loss through several molecular mechanisms. Body and muscle weights, limb muscle force, protein degradation and the ubiquitin-proteasome system, signaling pathways, oxidative stress and inflammation, autophagy, contractile and functional proteins, myostatin and myogenin, and muscle structure were evaluated in the diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing cachectic mice (BALB/c), with and without concomitant treatment with NF-kB (sulfasalazine), MAPK (U0126), and proteasome (bortezomib) inhibitors. Compared to control animals, in both respiratory and limb muscles of LC cachectic mice: muscle proteolysis, ubiquitinated proteins, autophagy, myostatin, protein oxidation, FoxO-1, NF-kB and MAPK signaling pathways, and muscle abnormalities were increased, while myosin, creatine kinase, myogenin, and slow- and fast-twitch muscle fiber size were decreased. Pharmacological inhibition of NF-kB and MAPK, but not the proteasome system, induced in cancer-induced cachectic animals, a substantial restoration of muscle mass and force through a decrease in muscle protein oxidation and catabolism, myostatin, and autophagy, together with a greater content of myogenin, and contractile and functional proteins. These findings may offer new therapeutic strategies in cancer-induced cachexia.Fil: Chacon Cabrera, Alba. Universitat Pompeu Fabra; España. Universidad Carlos III de Madrid. Instituto de Salud; EspañaFil: Fermoselle, Clara. Universitat Pompeu Fabra; España. Universidad Carlos III de Madrid. Instituto de Salud; EspañaFil: Urtreger, Alejandro Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Mateu Jimenez, Mercè. Universidad Carlos III de Madrid. Instituto de Salud; España. Universitat Pompeu Fabra; EspañaFil: Diament, Miriam. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; ArgentinaFil: Bal, Elisa Dora. 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: Sandri, Marco. Università di Padova; ItaliaFil: Barreiro, Eshter. Universitat Pompeu Fabra; España. Universidad Carlos III de Madrid. Instituto de Salud; EspañaWiley2014-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/30354Chacon Cabrera, Alba; Fermoselle, Clara; Urtreger, Alejandro Jorge; Mateu Jimenez, Mercè; Diament, Miriam; et al.; Pharmacological strategies in lung cancer-induced cachexia: effects on muscle proteolysis, autophagy, structure, and weakness; Wiley; Journal of Cellular Physiology; 229; 11; 7-2014; 1660-16720021-95411097-4652CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/jcp.24611info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:27Zoai:ri.conicet.gov.ar:11336/30354instacron: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 09:51:27.685CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Pharmacological strategies in lung cancer-induced cachexia: effects on muscle proteolysis, autophagy, structure, and weakness
title Pharmacological strategies in lung cancer-induced cachexia: effects on muscle proteolysis, autophagy, structure, and weakness
spellingShingle Pharmacological strategies in lung cancer-induced cachexia: effects on muscle proteolysis, autophagy, structure, and weakness
Chacon Cabrera, Alba
Lung Cancer
Cachexia
Pharmacology
Autophagy
title_short Pharmacological strategies in lung cancer-induced cachexia: effects on muscle proteolysis, autophagy, structure, and weakness
title_full Pharmacological strategies in lung cancer-induced cachexia: effects on muscle proteolysis, autophagy, structure, and weakness
title_fullStr Pharmacological strategies in lung cancer-induced cachexia: effects on muscle proteolysis, autophagy, structure, and weakness
title_full_unstemmed Pharmacological strategies in lung cancer-induced cachexia: effects on muscle proteolysis, autophagy, structure, and weakness
title_sort Pharmacological strategies in lung cancer-induced cachexia: effects on muscle proteolysis, autophagy, structure, and weakness
dc.creator.none.fl_str_mv Chacon Cabrera, Alba
Fermoselle, Clara
Urtreger, Alejandro Jorge
Mateu Jimenez, Mercè
Diament, Miriam
Bal, Elisa Dora
Sandri, Marco
Barreiro, Eshter
author Chacon Cabrera, Alba
author_facet Chacon Cabrera, Alba
Fermoselle, Clara
Urtreger, Alejandro Jorge
Mateu Jimenez, Mercè
Diament, Miriam
Bal, Elisa Dora
Sandri, Marco
Barreiro, Eshter
author_role author
author2 Fermoselle, Clara
Urtreger, Alejandro Jorge
Mateu Jimenez, Mercè
Diament, Miriam
Bal, Elisa Dora
Sandri, Marco
Barreiro, Eshter
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Lung Cancer
Cachexia
Pharmacology
Autophagy
topic Lung Cancer
Cachexia
Pharmacology
Autophagy
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Muscle wasting and cachexia are important systemic manifestations of highly prevalent conditions including cancer. Inflammation, oxidative stress, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-kB, and mitogen activated protein kinases (MAPK) are involved in the pathophysiology of cancer cachexia. Currently available treatment is limited and data demonstrating effectiveness in in vivo models are lacking. Our objectives were to explore in respiratory and limb muscles of lung cancer (LC) cachectic mice whether proteasome, NF-kB, and MAPK inhibitors improve muscle mass and function loss through several molecular mechanisms. Body and muscle weights, limb muscle force, protein degradation and the ubiquitin-proteasome system, signaling pathways, oxidative stress and inflammation, autophagy, contractile and functional proteins, myostatin and myogenin, and muscle structure were evaluated in the diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing cachectic mice (BALB/c), with and without concomitant treatment with NF-kB (sulfasalazine), MAPK (U0126), and proteasome (bortezomib) inhibitors. Compared to control animals, in both respiratory and limb muscles of LC cachectic mice: muscle proteolysis, ubiquitinated proteins, autophagy, myostatin, protein oxidation, FoxO-1, NF-kB and MAPK signaling pathways, and muscle abnormalities were increased, while myosin, creatine kinase, myogenin, and slow- and fast-twitch muscle fiber size were decreased. Pharmacological inhibition of NF-kB and MAPK, but not the proteasome system, induced in cancer-induced cachectic animals, a substantial restoration of muscle mass and force through a decrease in muscle protein oxidation and catabolism, myostatin, and autophagy, together with a greater content of myogenin, and contractile and functional proteins. These findings may offer new therapeutic strategies in cancer-induced cachexia.
Fil: Chacon Cabrera, Alba. Universitat Pompeu Fabra; España. Universidad Carlos III de Madrid. Instituto de Salud; España
Fil: Fermoselle, Clara. Universitat Pompeu Fabra; España. Universidad Carlos III de Madrid. Instituto de Salud; España
Fil: Urtreger, Alejandro Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Mateu Jimenez, Mercè. Universidad Carlos III de Madrid. Instituto de Salud; España. Universitat Pompeu Fabra; España
Fil: Diament, Miriam. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina
Fil: Bal, Elisa Dora. 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: Sandri, Marco. Università di Padova; Italia
Fil: Barreiro, Eshter. Universitat Pompeu Fabra; España. Universidad Carlos III de Madrid. Instituto de Salud; España
description Muscle wasting and cachexia are important systemic manifestations of highly prevalent conditions including cancer. Inflammation, oxidative stress, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-kB, and mitogen activated protein kinases (MAPK) are involved in the pathophysiology of cancer cachexia. Currently available treatment is limited and data demonstrating effectiveness in in vivo models are lacking. Our objectives were to explore in respiratory and limb muscles of lung cancer (LC) cachectic mice whether proteasome, NF-kB, and MAPK inhibitors improve muscle mass and function loss through several molecular mechanisms. Body and muscle weights, limb muscle force, protein degradation and the ubiquitin-proteasome system, signaling pathways, oxidative stress and inflammation, autophagy, contractile and functional proteins, myostatin and myogenin, and muscle structure were evaluated in the diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing cachectic mice (BALB/c), with and without concomitant treatment with NF-kB (sulfasalazine), MAPK (U0126), and proteasome (bortezomib) inhibitors. Compared to control animals, in both respiratory and limb muscles of LC cachectic mice: muscle proteolysis, ubiquitinated proteins, autophagy, myostatin, protein oxidation, FoxO-1, NF-kB and MAPK signaling pathways, and muscle abnormalities were increased, while myosin, creatine kinase, myogenin, and slow- and fast-twitch muscle fiber size were decreased. Pharmacological inhibition of NF-kB and MAPK, but not the proteasome system, induced in cancer-induced cachectic animals, a substantial restoration of muscle mass and force through a decrease in muscle protein oxidation and catabolism, myostatin, and autophagy, together with a greater content of myogenin, and contractile and functional proteins. These findings may offer new therapeutic strategies in cancer-induced cachexia.
publishDate 2014
dc.date.none.fl_str_mv 2014-07
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/11336/30354
Chacon Cabrera, Alba; Fermoselle, Clara; Urtreger, Alejandro Jorge; Mateu Jimenez, Mercè; Diament, Miriam; et al.; Pharmacological strategies in lung cancer-induced cachexia: effects on muscle proteolysis, autophagy, structure, and weakness; Wiley; Journal of Cellular Physiology; 229; 11; 7-2014; 1660-1672
0021-9541
1097-4652
CONICET Digital
CONICET
url http://hdl.handle.net/11336/30354
identifier_str_mv Chacon Cabrera, Alba; Fermoselle, Clara; Urtreger, Alejandro Jorge; Mateu Jimenez, Mercè; Diament, Miriam; et al.; Pharmacological strategies in lung cancer-induced cachexia: effects on muscle proteolysis, autophagy, structure, and weakness; Wiley; Journal of Cellular Physiology; 229; 11; 7-2014; 1660-1672
0021-9541
1097-4652
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/jcp.24611
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
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
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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