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dc.contributor.authorRibas i Fortuny, Judit
dc.contributor.authorBettayeb, Karima
dc.contributor.authorFerandin, Yoan
dc.contributor.authorKnockaert, Marie
dc.contributor.authorGarrofé Ochoa, Xènia
dc.contributor.authorTotzke, Frank
dc.contributor.authorSchächtele, Christoph
dc.contributor.authorMester, Jan
dc.contributor.authorPolychronopoulos, Panagiotis
dc.contributor.authorMagiatis, Prokopios
dc.contributor.authorSkaltsounis, Alexios-Leandros
dc.contributor.authorBoix Torras, Jacint
dc.contributor.authorMeijer, Laurent
dc.date.accessioned2015-03-23T19:16:07Z
dc.date.available2015-03-23T19:16:07Z
dc.date.issued2006
dc.identifier.issn0950-9232
dc.identifier.urihttp://hdl.handle.net/10459.1/48094
dc.description.abstractIndirubin, an isomer of indigo, is a reported inhibitor of cyclin-dependent kinases (CDKs) and glycogen synthase kinase-3 (GSK-3) as well as an agonist of the aryl hydrocarbon receptor (AhR). Indirubin is the active ingredient of a traditional Chinese medicinal recipe used against chronic myelocytic leukemia. Numerous indirubin analogs have been synthesized to optimize this promising kinase inhibitor scaffold. We report here on the cellular effects of 7-bromoindirubin-3'-oxime (7BIO). In contrast to its 5-bromo- and 6-bromo- isomers, and to indirubin-3'-oxime, 7BIO has only a marginal inhibitory activity towards CDKs and GSK-3. Unexpectedly, 7BIO triggers a rapid cell death process distinct from apoptosis. 7-Bromoindirubin-3'-oxime induces the appearance of large pycnotic nuclei, without classical features of apoptosis such as chromatin condensation and nuclear fragmentation. 7-Bromoindirubin-3'-oxime-induced cell death is not accompanied by cytochrome c release neither by any measurable effector caspase activation. Furthermore, the death process is not altered either by the presence of Q-VD-OPh, a broad-spectrum caspase inhibitor, or the overexpression of Bcl-2 and Bcl-XL proteins. Neither AhR nor p53 is required during 7BIO-induced cell death. Thus, in contrast to previously described indirubins, 7BIO triggers the activation of non-apoptotic cell death, possibly through necroptosis or autophagy. Although their molecular targets remain to be identified, 7-substituted indirubins may constitute a new class of potential antitumor compounds that would retain their activity in cells refractory to apoptosis.
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.isformatofVersió postprint del document publicat a: https://doi.org/10.1038/sj.onc.1209648
dc.relation.ispartofOncogene, 2006, vol. 25, num. 47, p. 6304-6318
dc.rights(c) Nature Publishing Group, 2006
dc.subjectApoptosis
dc.subjectAutophagy
dc.subjectKinases
dc.subjectIndirubins
dc.subjectCaspases
dc.subject.classificationApoptosi
dc.subject.classificationProteïnes quinases
dc.subject.classificationCàncer
dc.subject.classificationAutofàgia
dc.subject.classificationMort cel·lular
dc.subject.otherApoptosis
dc.subject.otherProtein kinases
dc.subject.otherCancer
dc.subject.otherAutophagy
dc.subject.otherCell death
dc.title7-Bromoindirubin-3'-oxime induces caspase-independent cell death
dc.typeinfo:eu-repo/semantics/article
dc.date.updated2015-03-23T19:16:07Z
dc.identifier.idgrec009194
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.identifier.doihttps://doi.org/10.1038/sj.onc.1209648


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