A human ribonuclease induces apoptosis associated with p21WAF1/CIP1 induction and JNK inactivation

Ribonucleases are promising agents for use in anticancer therapy. Among the different ribonucleases described to be cytotoxic, a paradigmatic example is onconase which manifests cytotoxic and cytostatic effects, presents synergism with several kinds of anticancer drugs and is currently in phase II/I...

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Autores: Castro Gallegos, Jessica, Ribó i Panosa, Marc, Navarro, Susanna, Nogués, Maria Victòria, Vilanova i Brugués, Maria, Benito i Mundet, Antoni
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2011
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/3929
Acceso en línea:http://hdl.handle.net/10256/3929
Access Level:acceso abierto
Palabra clave:Càncer -- Tractament
Ribonucleases
Cancer -- Treatment
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spelling A human ribonuclease induces apoptosis associated with p21WAF1/CIP1 induction and JNK inactivationCastro Gallegos, JessicaRibó i Panosa, MarcNavarro, SusannaNogués, Maria VictòriaVilanova i Brugués, MariaBenito i Mundet, AntoniCàncer -- TractamentRibonucleasesCancer -- TreatmentRibonucleases are promising agents for use in anticancer therapy. Among the different ribonucleases described to be cytotoxic, a paradigmatic example is onconase which manifests cytotoxic and cytostatic effects, presents synergism with several kinds of anticancer drugs and is currently in phase II/III of its clinical trial as an anticancer drug against different types of cancer. The mechanism of cytotoxicity of PE5, a variant of human pancreatic ribonuclease carrying a nuclear localization signal, has been investigated and compared to that of onconase. Methods: Cytotoxicity was measured by the MTT method and by the tripan blue exclusion assay. Apoptosis was assessed by flow cytometry, caspase enzymatic detection and confocal microscopy. Cell cycle phase analysis was performed by flow cytometry. The expression of different proteins was analyzed by western blot.n Results: We show that the cytotoxicity of PE5 is produced through apoptosis, that it does not require the proapoptotic activity of p53 and is not prevented by the multiple drug resistance phenotype. We also show that PE5 and onconase induce cell death at the same extent although the latter is also able to arrest the cell growth. We have compared the cytotoxic effects of both ribonucleases in the NCI/ADR-RES cell line by measuring their effects on the cell cycle, on the activation of different caspases and on the expression of different apoptosis- and cell cycle-related proteins. PE5 increases the number of cells in S and G2/M cell cycle phases, which is accompanied by the increased expression of cyclin E and p21WAF1/CIP1 together with the underphosphorylation of p46 forms of JNK. Citotoxicity of onconase in this cell line does not alter the cell cycle phase distribution and it is accompanied by a decreased expression of XIAP. Conclusions: We conclude that PE5 kills the cells through apoptosis associated with the p21WAF1/CIP1 induction and the inactivation of JNK. This mechanism is significantly different from that found for onconaseBioMed Central2011info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10256/3929http://hdl.handle.net/10256/3929BMC Cancer, 2011, vol. 11, núm. 9Articles publicats (D-B)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.1186/1471-2407-11-9info:eu-repo/semantics/altIdentifier/issn/1471-2407info:eu-repo/semantics/altIdentifier/eissn/1471-2407Aquest document està subjecte a una llicència Creative Commons: Reconeixement (by)http://creativecommons.org/licenses/by/2.0/es/deed.cainfo:eu-repo/semantics/openAccessoai:recercat.cat:10256/39292026-05-29T05:05:01Z
dc.title.none.fl_str_mv A human ribonuclease induces apoptosis associated with p21WAF1/CIP1 induction and JNK inactivation
title A human ribonuclease induces apoptosis associated with p21WAF1/CIP1 induction and JNK inactivation
spellingShingle A human ribonuclease induces apoptosis associated with p21WAF1/CIP1 induction and JNK inactivation
Castro Gallegos, Jessica
Càncer -- Tractament
Ribonucleases
Cancer -- Treatment
title_short A human ribonuclease induces apoptosis associated with p21WAF1/CIP1 induction and JNK inactivation
title_full A human ribonuclease induces apoptosis associated with p21WAF1/CIP1 induction and JNK inactivation
title_fullStr A human ribonuclease induces apoptosis associated with p21WAF1/CIP1 induction and JNK inactivation
title_full_unstemmed A human ribonuclease induces apoptosis associated with p21WAF1/CIP1 induction and JNK inactivation
title_sort A human ribonuclease induces apoptosis associated with p21WAF1/CIP1 induction and JNK inactivation
dc.creator.none.fl_str_mv Castro Gallegos, Jessica
Ribó i Panosa, Marc
Navarro, Susanna
Nogués, Maria Victòria
Vilanova i Brugués, Maria
Benito i Mundet, Antoni
author Castro Gallegos, Jessica
author_facet Castro Gallegos, Jessica
Ribó i Panosa, Marc
Navarro, Susanna
Nogués, Maria Victòria
Vilanova i Brugués, Maria
Benito i Mundet, Antoni
author_role author
author2 Ribó i Panosa, Marc
Navarro, Susanna
Nogués, Maria Victòria
Vilanova i Brugués, Maria
Benito i Mundet, Antoni
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Càncer -- Tractament
Ribonucleases
Cancer -- Treatment
topic Càncer -- Tractament
Ribonucleases
Cancer -- Treatment
description Ribonucleases are promising agents for use in anticancer therapy. Among the different ribonucleases described to be cytotoxic, a paradigmatic example is onconase which manifests cytotoxic and cytostatic effects, presents synergism with several kinds of anticancer drugs and is currently in phase II/III of its clinical trial as an anticancer drug against different types of cancer. The mechanism of cytotoxicity of PE5, a variant of human pancreatic ribonuclease carrying a nuclear localization signal, has been investigated and compared to that of onconase. Methods: Cytotoxicity was measured by the MTT method and by the tripan blue exclusion assay. Apoptosis was assessed by flow cytometry, caspase enzymatic detection and confocal microscopy. Cell cycle phase analysis was performed by flow cytometry. The expression of different proteins was analyzed by western blot.n Results: We show that the cytotoxicity of PE5 is produced through apoptosis, that it does not require the proapoptotic activity of p53 and is not prevented by the multiple drug resistance phenotype. We also show that PE5 and onconase induce cell death at the same extent although the latter is also able to arrest the cell growth. We have compared the cytotoxic effects of both ribonucleases in the NCI/ADR-RES cell line by measuring their effects on the cell cycle, on the activation of different caspases and on the expression of different apoptosis- and cell cycle-related proteins. PE5 increases the number of cells in S and G2/M cell cycle phases, which is accompanied by the increased expression of cyclin E and p21WAF1/CIP1 together with the underphosphorylation of p46 forms of JNK. Citotoxicity of onconase in this cell line does not alter the cell cycle phase distribution and it is accompanied by a decreased expression of XIAP. Conclusions: We conclude that PE5 kills the cells through apoptosis associated with the p21WAF1/CIP1 induction and the inactivation of JNK. This mechanism is significantly different from that found for onconase
publishDate 2011
dc.date.none.fl_str_mv 2011
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10256/3929
http://hdl.handle.net/10256/3929
url http://hdl.handle.net/10256/3929
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1186/1471-2407-11-9
info:eu-repo/semantics/altIdentifier/issn/1471-2407
info:eu-repo/semantics/altIdentifier/eissn/1471-2407
dc.rights.none.fl_str_mv Aquest document està subjecte a una llicència Creative Commons: Reconeixement (by)
http://creativecommons.org/licenses/by/2.0/es/deed.ca
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Aquest document està subjecte a una llicència Creative Commons: Reconeixement (by)
http://creativecommons.org/licenses/by/2.0/es/deed.ca
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv BMC Cancer, 2011, vol. 11, núm. 9
Articles publicats (D-B)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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