CIGB-300, an anti-CK2 peptide, inhibits angiogenesis, tumor cell invasion and metastasis in lung cancer models

Autores
Benavent Acero, Fernando Rodrigo; Capobianco, Carla Sabrina; Garona, Juan; Cirigliano, Stéfano Martín; Perera, Yasser; Urtreger, Alejandro Jorge; Perea, Silvio E.; Alonso, Daniel Fernando; Farina, Hernán Gabriel
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objectives: Casein kinase 2 (CK2) is overexpressed in several types of cancer. It has more than 300 substrates mainly involved in DNA reparation and replication, chromatin remodeling and cellular growth. In recent years CK2 became an interesting target for anticancer drug development. CIGB-300 is a peptidic inhibitor of CK2 activity, designed to bind to the phospho-acceptor domain of CK2 substrates, impairing the correct phosphorylation by the enzyme. The aim of this work was to explore the antitumor effects of this inhibitor in preclinical lung cancer models. Materials and methods: Human H125 and murine 3LL Lewis lung carcinoma cell lines were used to evaluate the effect of CIGB-300 treatment in vitro. For this purpose, adhesion, migration and invasion capabilities of cancer cells were tested. Proteolytic activity of tumor cell-secreted uPA and MMP after CIGB-300 incubation was also analyzed. In vivo anticancer efficacy of the peptide was evaluated using experimental and spontaneous lung colonization assays in C57BL/6 mice. Finally, in order to test the effect of CIGB-300 on tumor cell-induced angiogenesis, a modified Matrigel plug assay was conducted. Results and conclusion: We demonstrate that treatment with low micromolar concentrations of CIGB-300 caused a drastic reduction of adhesion, migration and invasion of lung cancer cells. Reduced invasiveness after CIGB-300 incubation was associated with decreased proteolytic activity of tumor cell-conditioned medium. In vivo, intravenous administration of CIGB-300 (10 mg/kg) markly decreased lung colonization and metastasis development of 3LL cells. Interestingly, after 5 days of systemic treatment with CIGB-300, tumor cell-driven neovascularization was significantly reduced in comparison to control group. Altogether our data suggest an important role of CK2 in lung tumor development, suggesting a potential use of CIGB-300 as a novel therapeutic agent against lung cancer.
Fil: Benavent Acero, Fernando Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Capobianco, Carla Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Garona, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Cirigliano, Stéfano Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina
Fil: Perera, Yasser. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Urtreger, Alejandro Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Perea, Silvio E.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Farina, Hernán Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Materia
ANGIOGENESIS
CIGB-300
CK2
LUNG CANCER
METASTASIS
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:11336/72190
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/72190
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling CIGB-300, an anti-CK2 peptide, inhibits angiogenesis, tumor cell invasion and metastasis in lung cancer modelsBenavent Acero, Fernando RodrigoCapobianco, Carla SabrinaGarona, JuanCirigliano, Stéfano MartínPerera, YasserUrtreger, Alejandro JorgePerea, Silvio E.Alonso, Daniel FernandoFarina, Hernán GabrielANGIOGENESISCIGB-300CK2LUNG CANCERMETASTASIShttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Objectives: Casein kinase 2 (CK2) is overexpressed in several types of cancer. It has more than 300 substrates mainly involved in DNA reparation and replication, chromatin remodeling and cellular growth. In recent years CK2 became an interesting target for anticancer drug development. CIGB-300 is a peptidic inhibitor of CK2 activity, designed to bind to the phospho-acceptor domain of CK2 substrates, impairing the correct phosphorylation by the enzyme. The aim of this work was to explore the antitumor effects of this inhibitor in preclinical lung cancer models. Materials and methods: Human H125 and murine 3LL Lewis lung carcinoma cell lines were used to evaluate the effect of CIGB-300 treatment in vitro. For this purpose, adhesion, migration and invasion capabilities of cancer cells were tested. Proteolytic activity of tumor cell-secreted uPA and MMP after CIGB-300 incubation was also analyzed. In vivo anticancer efficacy of the peptide was evaluated using experimental and spontaneous lung colonization assays in C57BL/6 mice. Finally, in order to test the effect of CIGB-300 on tumor cell-induced angiogenesis, a modified Matrigel plug assay was conducted. Results and conclusion: We demonstrate that treatment with low micromolar concentrations of CIGB-300 caused a drastic reduction of adhesion, migration and invasion of lung cancer cells. Reduced invasiveness after CIGB-300 incubation was associated with decreased proteolytic activity of tumor cell-conditioned medium. In vivo, intravenous administration of CIGB-300 (10 mg/kg) markly decreased lung colonization and metastasis development of 3LL cells. Interestingly, after 5 days of systemic treatment with CIGB-300, tumor cell-driven neovascularization was significantly reduced in comparison to control group. Altogether our data suggest an important role of CK2 in lung tumor development, suggesting a potential use of CIGB-300 as a novel therapeutic agent against lung cancer.Fil: Benavent Acero, Fernando Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Capobianco, Carla Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Garona, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Cirigliano, Stéfano Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; ArgentinaFil: Perera, Yasser. Centro de Ingeniería Genética y Biotecnología; CubaFil: Urtreger, Alejandro Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Perea, Silvio E.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Farina, Hernán Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaElsevier Ireland2017-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/72190Benavent Acero, Fernando Rodrigo; Capobianco, Carla Sabrina; Garona, Juan; Cirigliano, Stéfano Martín; Perera, Yasser; et al.; CIGB-300, an anti-CK2 peptide, inhibits angiogenesis, tumor cell invasion and metastasis in lung cancer models; Elsevier Ireland; Lung Cancer; 107; 5-2017; 14-210169-5002CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S016950021630352Xinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.lungcan.2016.05.026info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T10:52:22Zoai:ri.conicet.gov.ar:11336/72190instacron: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:34982025-09-17 10:52:23.054CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv CIGB-300, an anti-CK2 peptide, inhibits angiogenesis, tumor cell invasion and metastasis in lung cancer models
title CIGB-300, an anti-CK2 peptide, inhibits angiogenesis, tumor cell invasion and metastasis in lung cancer models
spellingShingle CIGB-300, an anti-CK2 peptide, inhibits angiogenesis, tumor cell invasion and metastasis in lung cancer models
Benavent Acero, Fernando Rodrigo
ANGIOGENESIS
CIGB-300
CK2
LUNG CANCER
METASTASIS
title_short CIGB-300, an anti-CK2 peptide, inhibits angiogenesis, tumor cell invasion and metastasis in lung cancer models
title_full CIGB-300, an anti-CK2 peptide, inhibits angiogenesis, tumor cell invasion and metastasis in lung cancer models
title_fullStr CIGB-300, an anti-CK2 peptide, inhibits angiogenesis, tumor cell invasion and metastasis in lung cancer models
title_full_unstemmed CIGB-300, an anti-CK2 peptide, inhibits angiogenesis, tumor cell invasion and metastasis in lung cancer models
title_sort CIGB-300, an anti-CK2 peptide, inhibits angiogenesis, tumor cell invasion and metastasis in lung cancer models
dc.creator.none.fl_str_mv Benavent Acero, Fernando Rodrigo
Capobianco, Carla Sabrina
Garona, Juan
Cirigliano, Stéfano Martín
Perera, Yasser
Urtreger, Alejandro Jorge
Perea, Silvio E.
Alonso, Daniel Fernando
Farina, Hernán Gabriel
author Benavent Acero, Fernando Rodrigo
author_facet Benavent Acero, Fernando Rodrigo
Capobianco, Carla Sabrina
Garona, Juan
Cirigliano, Stéfano Martín
Perera, Yasser
Urtreger, Alejandro Jorge
Perea, Silvio E.
Alonso, Daniel Fernando
Farina, Hernán Gabriel
author_role author
author2 Capobianco, Carla Sabrina
Garona, Juan
Cirigliano, Stéfano Martín
Perera, Yasser
Urtreger, Alejandro Jorge
Perea, Silvio E.
Alonso, Daniel Fernando
Farina, Hernán Gabriel
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ANGIOGENESIS
CIGB-300
CK2
LUNG CANCER
METASTASIS
topic ANGIOGENESIS
CIGB-300
CK2
LUNG CANCER
METASTASIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objectives: Casein kinase 2 (CK2) is overexpressed in several types of cancer. It has more than 300 substrates mainly involved in DNA reparation and replication, chromatin remodeling and cellular growth. In recent years CK2 became an interesting target for anticancer drug development. CIGB-300 is a peptidic inhibitor of CK2 activity, designed to bind to the phospho-acceptor domain of CK2 substrates, impairing the correct phosphorylation by the enzyme. The aim of this work was to explore the antitumor effects of this inhibitor in preclinical lung cancer models. Materials and methods: Human H125 and murine 3LL Lewis lung carcinoma cell lines were used to evaluate the effect of CIGB-300 treatment in vitro. For this purpose, adhesion, migration and invasion capabilities of cancer cells were tested. Proteolytic activity of tumor cell-secreted uPA and MMP after CIGB-300 incubation was also analyzed. In vivo anticancer efficacy of the peptide was evaluated using experimental and spontaneous lung colonization assays in C57BL/6 mice. Finally, in order to test the effect of CIGB-300 on tumor cell-induced angiogenesis, a modified Matrigel plug assay was conducted. Results and conclusion: We demonstrate that treatment with low micromolar concentrations of CIGB-300 caused a drastic reduction of adhesion, migration and invasion of lung cancer cells. Reduced invasiveness after CIGB-300 incubation was associated with decreased proteolytic activity of tumor cell-conditioned medium. In vivo, intravenous administration of CIGB-300 (10 mg/kg) markly decreased lung colonization and metastasis development of 3LL cells. Interestingly, after 5 days of systemic treatment with CIGB-300, tumor cell-driven neovascularization was significantly reduced in comparison to control group. Altogether our data suggest an important role of CK2 in lung tumor development, suggesting a potential use of CIGB-300 as a novel therapeutic agent against lung cancer.
Fil: Benavent Acero, Fernando Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Capobianco, Carla Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Garona, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Cirigliano, Stéfano Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina
Fil: Perera, Yasser. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Urtreger, Alejandro Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Perea, Silvio E.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Farina, Hernán Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
description Objectives: Casein kinase 2 (CK2) is overexpressed in several types of cancer. It has more than 300 substrates mainly involved in DNA reparation and replication, chromatin remodeling and cellular growth. In recent years CK2 became an interesting target for anticancer drug development. CIGB-300 is a peptidic inhibitor of CK2 activity, designed to bind to the phospho-acceptor domain of CK2 substrates, impairing the correct phosphorylation by the enzyme. The aim of this work was to explore the antitumor effects of this inhibitor in preclinical lung cancer models. Materials and methods: Human H125 and murine 3LL Lewis lung carcinoma cell lines were used to evaluate the effect of CIGB-300 treatment in vitro. For this purpose, adhesion, migration and invasion capabilities of cancer cells were tested. Proteolytic activity of tumor cell-secreted uPA and MMP after CIGB-300 incubation was also analyzed. In vivo anticancer efficacy of the peptide was evaluated using experimental and spontaneous lung colonization assays in C57BL/6 mice. Finally, in order to test the effect of CIGB-300 on tumor cell-induced angiogenesis, a modified Matrigel plug assay was conducted. Results and conclusion: We demonstrate that treatment with low micromolar concentrations of CIGB-300 caused a drastic reduction of adhesion, migration and invasion of lung cancer cells. Reduced invasiveness after CIGB-300 incubation was associated with decreased proteolytic activity of tumor cell-conditioned medium. In vivo, intravenous administration of CIGB-300 (10 mg/kg) markly decreased lung colonization and metastasis development of 3LL cells. Interestingly, after 5 days of systemic treatment with CIGB-300, tumor cell-driven neovascularization was significantly reduced in comparison to control group. Altogether our data suggest an important role of CK2 in lung tumor development, suggesting a potential use of CIGB-300 as a novel therapeutic agent against lung cancer.
publishDate 2017
dc.date.none.fl_str_mv 2017-05
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/11336/72190
Benavent Acero, Fernando Rodrigo; Capobianco, Carla Sabrina; Garona, Juan; Cirigliano, Stéfano Martín; Perera, Yasser; et al.; CIGB-300, an anti-CK2 peptide, inhibits angiogenesis, tumor cell invasion and metastasis in lung cancer models; Elsevier Ireland; Lung Cancer; 107; 5-2017; 14-21
0169-5002
CONICET Digital
CONICET
url http://hdl.handle.net/11336/72190
identifier_str_mv Benavent Acero, Fernando Rodrigo; Capobianco, Carla Sabrina; Garona, Juan; Cirigliano, Stéfano Martín; Perera, Yasser; et al.; CIGB-300, an anti-CK2 peptide, inhibits angiogenesis, tumor cell invasion and metastasis in lung cancer models; Elsevier Ireland; Lung Cancer; 107; 5-2017; 14-21
0169-5002
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.sciencedirect.com/science/article/pii/S016950021630352X
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.lungcan.2016.05.026
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
application/pdf
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
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 13.000565

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