Sensitivity of tumor cells towards CIGB-300 anticancer peptide relies on its nucleolar localization

Autores
Perera, Yasser; Costales, Heydi C.; Diaz, Yakelin; Reyes, Osvaldo; Farina, Hernán Gabriel; Mendez, Lissandra; Gómez, Roberto E.; Acevedo, Boris E.; Gomez, Daniel Eduardo; Alonso, Daniel Fernando; Perea, Silvio E.
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
CIGB-300 is a novel anticancer peptide that impairs the casein kinase 2-mediated phosphorylation by direct binding to the conserved phosphoacceptor site on their substrates. Previous findings indicated that CIGB-300 inhibits tumor cell proliferation in vitro and induces tumor growth delay in vivo in cancer animal models. Interestingly, we had previously demonstrated that the putative oncogene B23/nucleophosmin (NPM) is the major intracellular target for CIGB-300 in a sensitive human lung cancer cell line. However, the ability of this peptide to target B23/NPM in cancer cells with differential CIGB-300 response phenotype remained to be determined. Interestingly, in this work, we evidenced that CIGB-300's antiproliferative activity on tumor cells strongly correlates with its nucleolar localization, the main subcellular localization of the previously identified B23/NPM target. Likewise, using CIGB-300 equipotent doses (concentration that inhibits 50% of proliferation), we demonstrated that this peptide interacts and inhibits B23/NPM phosphorylation in different cancer cell lines as evidenced by in vivo pull-down and metabolic labeling experiments. Moreover, such inhibition was followed by a fast apoptosis on CIGB-300-treated cells and also an impairment of cell cycle progression mainly after 5 h of treatment. Altogether, our data not only validates B23/NPM as a main target for CIGB-300 in cancer cells but also provides the first experimental clues to explain their differential antiproliferative response. Importantly, our findings suggest that further improvements to this cell penetrating peptide-based drug should entail its more efficient intracellular delivery at such subcellular localization.
Fil: Perera, Yasser. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Costales, Heydi C.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Diaz, Yakelin. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Reyes, Osvaldo. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Farina, Hernán Gabriel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mendez, Lissandra. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Gómez, Roberto E.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Acevedo, Boris E.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Perea, Silvio E.. Centro de Ingeniería Genética y Biotecnología; Cuba
Materia
B23/NUCLEOPHOSMIN
CELL PENETRATING PEPTIDE
CIGB-300
CK2
P15-TAT
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:11336/192586
Acceder
id CONICETDig_244fd638bc2cb70286ef5fbe1ffddfe5
oai_identifier_str oai:ri.conicet.gov.ar:11336/192586
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Sensitivity of tumor cells towards CIGB-300 anticancer peptide relies on its nucleolar localizationPerera, YasserCostales, Heydi C.Diaz, YakelinReyes, OsvaldoFarina, Hernán GabrielMendez, LissandraGómez, Roberto E.Acevedo, Boris E.Gomez, Daniel EduardoAlonso, Daniel FernandoPerea, Silvio E.B23/NUCLEOPHOSMINCELL PENETRATING PEPTIDECIGB-300CK2P15-TAThttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3CIGB-300 is a novel anticancer peptide that impairs the casein kinase 2-mediated phosphorylation by direct binding to the conserved phosphoacceptor site on their substrates. Previous findings indicated that CIGB-300 inhibits tumor cell proliferation in vitro and induces tumor growth delay in vivo in cancer animal models. Interestingly, we had previously demonstrated that the putative oncogene B23/nucleophosmin (NPM) is the major intracellular target for CIGB-300 in a sensitive human lung cancer cell line. However, the ability of this peptide to target B23/NPM in cancer cells with differential CIGB-300 response phenotype remained to be determined. Interestingly, in this work, we evidenced that CIGB-300's antiproliferative activity on tumor cells strongly correlates with its nucleolar localization, the main subcellular localization of the previously identified B23/NPM target. Likewise, using CIGB-300 equipotent doses (concentration that inhibits 50% of proliferation), we demonstrated that this peptide interacts and inhibits B23/NPM phosphorylation in different cancer cell lines as evidenced by in vivo pull-down and metabolic labeling experiments. Moreover, such inhibition was followed by a fast apoptosis on CIGB-300-treated cells and also an impairment of cell cycle progression mainly after 5 h of treatment. Altogether, our data not only validates B23/NPM as a main target for CIGB-300 in cancer cells but also provides the first experimental clues to explain their differential antiproliferative response. Importantly, our findings suggest that further improvements to this cell penetrating peptide-based drug should entail its more efficient intracellular delivery at such subcellular localization.Fil: Perera, Yasser. Centro de Ingeniería Genética y Biotecnología; CubaFil: Costales, Heydi C.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Diaz, Yakelin. Centro de Ingeniería Genética y Biotecnología; CubaFil: Reyes, Osvaldo. Centro de Ingeniería Genética y Biotecnología; CubaFil: Farina, Hernán Gabriel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mendez, Lissandra. Centro de Ingeniería Genética y Biotecnología; CubaFil: Gómez, Roberto E.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Acevedo, Boris E.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Perea, Silvio E.. Centro de Ingeniería Genética y Biotecnología; CubaJohn Wiley & Sons Ltd2012-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/192586Perera, Yasser; Costales, Heydi C.; Diaz, Yakelin; Reyes, Osvaldo; Farina, Hernán Gabriel; et al.; Sensitivity of tumor cells towards CIGB-300 anticancer peptide relies on its nucleolar localization; John Wiley & Sons Ltd; Journal Of Peptide Science; 18; 4; 4-2012; 215-2231075-2617CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/psc.1432info:eu-repo/semantics/altIdentifier/doi/10.1002/psc.1432info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-05T09:56:02Zoai:ri.conicet.gov.ar:11336/192586instacron: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:34982025-11-05 09:56:03.095CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Sensitivity of tumor cells towards CIGB-300 anticancer peptide relies on its nucleolar localization
title Sensitivity of tumor cells towards CIGB-300 anticancer peptide relies on its nucleolar localization
spellingShingle Sensitivity of tumor cells towards CIGB-300 anticancer peptide relies on its nucleolar localization
Perera, Yasser
B23/NUCLEOPHOSMIN
CELL PENETRATING PEPTIDE
CIGB-300
CK2
P15-TAT
title_short Sensitivity of tumor cells towards CIGB-300 anticancer peptide relies on its nucleolar localization
title_full Sensitivity of tumor cells towards CIGB-300 anticancer peptide relies on its nucleolar localization
title_fullStr Sensitivity of tumor cells towards CIGB-300 anticancer peptide relies on its nucleolar localization
title_full_unstemmed Sensitivity of tumor cells towards CIGB-300 anticancer peptide relies on its nucleolar localization
title_sort Sensitivity of tumor cells towards CIGB-300 anticancer peptide relies on its nucleolar localization
dc.creator.none.fl_str_mv Perera, Yasser
Costales, Heydi C.
Diaz, Yakelin
Reyes, Osvaldo
Farina, Hernán Gabriel
Mendez, Lissandra
Gómez, Roberto E.
Acevedo, Boris E.
Gomez, Daniel Eduardo
Alonso, Daniel Fernando
Perea, Silvio E.
author Perera, Yasser
author_facet Perera, Yasser
Costales, Heydi C.
Diaz, Yakelin
Reyes, Osvaldo
Farina, Hernán Gabriel
Mendez, Lissandra
Gómez, Roberto E.
Acevedo, Boris E.
Gomez, Daniel Eduardo
Alonso, Daniel Fernando
Perea, Silvio E.
author_role author
author2 Costales, Heydi C.
Diaz, Yakelin
Reyes, Osvaldo
Farina, Hernán Gabriel
Mendez, Lissandra
Gómez, Roberto E.
Acevedo, Boris E.
Gomez, Daniel Eduardo
Alonso, Daniel Fernando
Perea, Silvio E.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv B23/NUCLEOPHOSMIN
CELL PENETRATING PEPTIDE
CIGB-300
CK2
P15-TAT
topic B23/NUCLEOPHOSMIN
CELL PENETRATING PEPTIDE
CIGB-300
CK2
P15-TAT
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv CIGB-300 is a novel anticancer peptide that impairs the casein kinase 2-mediated phosphorylation by direct binding to the conserved phosphoacceptor site on their substrates. Previous findings indicated that CIGB-300 inhibits tumor cell proliferation in vitro and induces tumor growth delay in vivo in cancer animal models. Interestingly, we had previously demonstrated that the putative oncogene B23/nucleophosmin (NPM) is the major intracellular target for CIGB-300 in a sensitive human lung cancer cell line. However, the ability of this peptide to target B23/NPM in cancer cells with differential CIGB-300 response phenotype remained to be determined. Interestingly, in this work, we evidenced that CIGB-300's antiproliferative activity on tumor cells strongly correlates with its nucleolar localization, the main subcellular localization of the previously identified B23/NPM target. Likewise, using CIGB-300 equipotent doses (concentration that inhibits 50% of proliferation), we demonstrated that this peptide interacts and inhibits B23/NPM phosphorylation in different cancer cell lines as evidenced by in vivo pull-down and metabolic labeling experiments. Moreover, such inhibition was followed by a fast apoptosis on CIGB-300-treated cells and also an impairment of cell cycle progression mainly after 5 h of treatment. Altogether, our data not only validates B23/NPM as a main target for CIGB-300 in cancer cells but also provides the first experimental clues to explain their differential antiproliferative response. Importantly, our findings suggest that further improvements to this cell penetrating peptide-based drug should entail its more efficient intracellular delivery at such subcellular localization.
Fil: Perera, Yasser. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Costales, Heydi C.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Diaz, Yakelin. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Reyes, Osvaldo. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Farina, Hernán Gabriel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mendez, Lissandra. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Gómez, Roberto E.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Acevedo, Boris E.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Perea, Silvio E.. Centro de Ingeniería Genética y Biotecnología; Cuba
description CIGB-300 is a novel anticancer peptide that impairs the casein kinase 2-mediated phosphorylation by direct binding to the conserved phosphoacceptor site on their substrates. Previous findings indicated that CIGB-300 inhibits tumor cell proliferation in vitro and induces tumor growth delay in vivo in cancer animal models. Interestingly, we had previously demonstrated that the putative oncogene B23/nucleophosmin (NPM) is the major intracellular target for CIGB-300 in a sensitive human lung cancer cell line. However, the ability of this peptide to target B23/NPM in cancer cells with differential CIGB-300 response phenotype remained to be determined. Interestingly, in this work, we evidenced that CIGB-300's antiproliferative activity on tumor cells strongly correlates with its nucleolar localization, the main subcellular localization of the previously identified B23/NPM target. Likewise, using CIGB-300 equipotent doses (concentration that inhibits 50% of proliferation), we demonstrated that this peptide interacts and inhibits B23/NPM phosphorylation in different cancer cell lines as evidenced by in vivo pull-down and metabolic labeling experiments. Moreover, such inhibition was followed by a fast apoptosis on CIGB-300-treated cells and also an impairment of cell cycle progression mainly after 5 h of treatment. Altogether, our data not only validates B23/NPM as a main target for CIGB-300 in cancer cells but also provides the first experimental clues to explain their differential antiproliferative response. Importantly, our findings suggest that further improvements to this cell penetrating peptide-based drug should entail its more efficient intracellular delivery at such subcellular localization.
publishDate 2012
dc.date.none.fl_str_mv 2012-04
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/11336/192586
Perera, Yasser; Costales, Heydi C.; Diaz, Yakelin; Reyes, Osvaldo; Farina, Hernán Gabriel; et al.; Sensitivity of tumor cells towards CIGB-300 anticancer peptide relies on its nucleolar localization; John Wiley & Sons Ltd; Journal Of Peptide Science; 18; 4; 4-2012; 215-223
1075-2617
CONICET Digital
CONICET
url http://hdl.handle.net/11336/192586
identifier_str_mv Perera, Yasser; Costales, Heydi C.; Diaz, Yakelin; Reyes, Osvaldo; Farina, Hernán Gabriel; et al.; Sensitivity of tumor cells towards CIGB-300 anticancer peptide relies on its nucleolar localization; John Wiley & Sons Ltd; Journal Of Peptide Science; 18; 4; 4-2012; 215-223
1075-2617
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://onlinelibrary.wiley.com/doi/10.1002/psc.1432
info:eu-repo/semantics/altIdentifier/doi/10.1002/psc.1432
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons Ltd
publisher.none.fl_str_mv John Wiley & Sons Ltd
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 13.087074

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