Cell differentiation, caspase inhibition and macromolecular synthesis blockage, but not Bcl-2 or Bcl-XL proteins, protect SH-SY5Y cells from apoptosis triggered by two cdk inhibitory drugs.

Olomoucine and Roscovitine are two ATP-competing compounds described as specific inhibitors of cyclin-dependent kinases (CDK). Both drugs showed to induce apoptosis in SH-SY5Y, a neuroblastoma-derived cell line. In these cells, neither Bcl-2 nor Bcl-XL overexpression conferred any resistance to both...

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Detalhes bibliográficos
Autores: Ribas i Fortuny, Judit, Boix Torras, Jacint
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2004
País:España
Recursos:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/48116
Acesso em linha:https://doi.org/10.1016/j.yexcr.2003.12.019
http://hdl.handle.net/10459.1/48116
Access Level:acceso abierto
Palavra-chave:Olomoucine
Roscovitine
CDK
Apoptosis
Cell Cycle
Apoptosi
Cicle cel·lular
Cell cycle
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spelling Cell differentiation, caspase inhibition and macromolecular synthesis blockage, but not Bcl-2 or Bcl-XL proteins, protect SH-SY5Y cells from apoptosis triggered by two cdk inhibitory drugs.Ribas i Fortuny, JuditBoix Torras, JacintOlomoucineRoscovitineCDKApoptosisCell CycleApoptosiCicle cel·lularApoptosisCell cycleOlomoucine and Roscovitine are two ATP-competing compounds described as specific inhibitors of cyclin-dependent kinases (CDK). Both drugs showed to induce apoptosis in SH-SY5Y, a neuroblastoma-derived cell line. In these cells, neither Bcl-2 nor Bcl-XL overexpression conferred any resistance to both drugs. However, a partial protective effect was detected when cells were treated with a general inhibitor of caspases (zVADfmk), cycloheximide (CHX), or actinomycin D (DAct). Interestingly, a synergism in cell protection was observed between zVADfmk and macromolecular synthesis inhibitors, thus suggesting different apoptotic pathways in distinct subpopulations of the cell culture. On the other hand, no lethality was found when cells were treated with either PD98059 or UO126. This discarded Erk1/Erk2 inhibition as the cause of apoptosis. Furthermore, SH-SY5Y cells became resistant to either Olomoucine or Roscovitine upon the induction of differentiation. This resistance correlated with the extent of differentiation and, therefore, the number of cells entering a quiescent state. In conclusion, our results seem to support a role for CDK inhibition as the cause of the apoptotic process triggered by Olomoucine and Roscovitine. In addition, we contribute to define a promising profile as anticancer drugs for both compounds, at least in the treatment of neuroblastoma.Elsevier2004info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://doi.org/10.1016/j.yexcr.2003.12.019http://hdl.handle.net/10459.1/48116reponame:Repositori Obert UdL instname:Universitat de Lleida (UdL)InglésVersió preprint del document publicat a: https://doi.org/10.1016/j.yexcr.2003.12.019Experimental Cell Research, 2004, vol. 295, num. 1, p. 9-24(c) Elsevier, 2004info:eu-repo/semantics/openAccessoai:repositori.udl.cat:10459.1/481162026-06-24T12:42:17Z
dc.title.none.fl_str_mv Cell differentiation, caspase inhibition and macromolecular synthesis blockage, but not Bcl-2 or Bcl-XL proteins, protect SH-SY5Y cells from apoptosis triggered by two cdk inhibitory drugs.
title Cell differentiation, caspase inhibition and macromolecular synthesis blockage, but not Bcl-2 or Bcl-XL proteins, protect SH-SY5Y cells from apoptosis triggered by two cdk inhibitory drugs.
spellingShingle Cell differentiation, caspase inhibition and macromolecular synthesis blockage, but not Bcl-2 or Bcl-XL proteins, protect SH-SY5Y cells from apoptosis triggered by two cdk inhibitory drugs.
Ribas i Fortuny, Judit
Olomoucine
Roscovitine
CDK
Apoptosis
Cell Cycle
Apoptosi
Cicle cel·lular
Apoptosis
Cell cycle
title_short Cell differentiation, caspase inhibition and macromolecular synthesis blockage, but not Bcl-2 or Bcl-XL proteins, protect SH-SY5Y cells from apoptosis triggered by two cdk inhibitory drugs.
title_full Cell differentiation, caspase inhibition and macromolecular synthesis blockage, but not Bcl-2 or Bcl-XL proteins, protect SH-SY5Y cells from apoptosis triggered by two cdk inhibitory drugs.
title_fullStr Cell differentiation, caspase inhibition and macromolecular synthesis blockage, but not Bcl-2 or Bcl-XL proteins, protect SH-SY5Y cells from apoptosis triggered by two cdk inhibitory drugs.
title_full_unstemmed Cell differentiation, caspase inhibition and macromolecular synthesis blockage, but not Bcl-2 or Bcl-XL proteins, protect SH-SY5Y cells from apoptosis triggered by two cdk inhibitory drugs.
title_sort Cell differentiation, caspase inhibition and macromolecular synthesis blockage, but not Bcl-2 or Bcl-XL proteins, protect SH-SY5Y cells from apoptosis triggered by two cdk inhibitory drugs.
dc.creator.none.fl_str_mv Ribas i Fortuny, Judit
Boix Torras, Jacint
author Ribas i Fortuny, Judit
author_facet Ribas i Fortuny, Judit
Boix Torras, Jacint
author_role author
author2 Boix Torras, Jacint
author2_role author
dc.subject.none.fl_str_mv Olomoucine
Roscovitine
CDK
Apoptosis
Cell Cycle
Apoptosi
Cicle cel·lular
Apoptosis
Cell cycle
topic Olomoucine
Roscovitine
CDK
Apoptosis
Cell Cycle
Apoptosi
Cicle cel·lular
Apoptosis
Cell cycle
description Olomoucine and Roscovitine are two ATP-competing compounds described as specific inhibitors of cyclin-dependent kinases (CDK). Both drugs showed to induce apoptosis in SH-SY5Y, a neuroblastoma-derived cell line. In these cells, neither Bcl-2 nor Bcl-XL overexpression conferred any resistance to both drugs. However, a partial protective effect was detected when cells were treated with a general inhibitor of caspases (zVADfmk), cycloheximide (CHX), or actinomycin D (DAct). Interestingly, a synergism in cell protection was observed between zVADfmk and macromolecular synthesis inhibitors, thus suggesting different apoptotic pathways in distinct subpopulations of the cell culture. On the other hand, no lethality was found when cells were treated with either PD98059 or UO126. This discarded Erk1/Erk2 inhibition as the cause of apoptosis. Furthermore, SH-SY5Y cells became resistant to either Olomoucine or Roscovitine upon the induction of differentiation. This resistance correlated with the extent of differentiation and, therefore, the number of cells entering a quiescent state. In conclusion, our results seem to support a role for CDK inhibition as the cause of the apoptotic process triggered by Olomoucine and Roscovitine. In addition, we contribute to define a promising profile as anticancer drugs for both compounds, at least in the treatment of neuroblastoma.
publishDate 2004
dc.date.none.fl_str_mv 2004
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1016/j.yexcr.2003.12.019
http://hdl.handle.net/10459.1/48116
url https://doi.org/10.1016/j.yexcr.2003.12.019
http://hdl.handle.net/10459.1/48116
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió preprint del document publicat a: https://doi.org/10.1016/j.yexcr.2003.12.019
Experimental Cell Research, 2004, vol. 295, num. 1, p. 9-24
dc.rights.none.fl_str_mv (c) Elsevier, 2004
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Elsevier, 2004
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositori Obert UdL
instname:Universitat de Lleida (UdL)
instname_str Universitat de Lleida (UdL)
reponame_str Repositori Obert UdL
collection Repositori Obert UdL
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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