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dc.contributor.authorRibas i Fortuny, Judit
dc.contributor.authorBoix Torras, Jacint
dc.date.accessioned2015-03-26T18:23:41Z
dc.date.available2015-03-26T18:23:41Z
dc.date.issued2004
dc.identifier.issn0014-4827
dc.identifier.urihttp://hdl.handle.net/10459.1/48116
dc.description.abstractOlomoucine 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.
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherElsevier
dc.relation.isformatofVersió preprint del document publicat a: https://doi.org/10.1016/j.yexcr.2003.12.019
dc.relation.ispartofExperimental Cell Research, 2004, vol. 295, num. 1, p. 9-24
dc.rights(c) Elsevier, 2004
dc.subjectOlomoucine
dc.subjectRoscovitine
dc.subjectCDK
dc.subjectApoptosis
dc.subjectCell Cycle
dc.subject.classificationApoptosi
dc.subject.classificationCicle cel·lular
dc.subject.otherApoptosis
dc.subject.otherCell cycle
dc.titleCell 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.typeinfo:eu-repo/semantics/article
dc.date.updated2015-03-26T18:23:41Z
dc.identifier.idgrec004839
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.identifier.doihttps://doi.org/10.1016/j.yexcr.2003.12.019


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