dc.contributor.author |
Ribas i Fortuny, Judit |
dc.contributor.author |
Bettayeb, Karima |
dc.contributor.author |
Ferandin, Yoan |
dc.contributor.author |
Knockaert, Marie |
dc.contributor.author |
Garrofé Ochoa, Xènia |
dc.contributor.author |
Totzke, Frank |
dc.contributor.author |
Schächtele, Christoph |
dc.contributor.author |
Mester, Jan |
dc.contributor.author |
Polychronopoulos, Panagiotis |
dc.contributor.author |
Magiatis, Prokopios |
dc.contributor.author |
Skaltsounis, Alexios-Leandros |
dc.contributor.author |
Boix Torras, Jacint |
dc.contributor.author |
Meijer, Laurent |
dc.date |
2015-03-23T19:16:07Z |
dc.date |
2015-03-23T19:16:07Z |
dc.date |
2006 |
dc.date |
2015-03-23T19:16:07Z |
dc.identifier |
0950-9232 |
dc.identifier |
http://hdl.handle.net/10459.1/48094 |
dc.identifier |
https://doi.org/10.1038/sj.onc.1209648 |
dc.identifier.uri |
http://hdl.handle.net/10459.1/48094 |
dc.description |
Indirubin, 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 |
application/pdf |
dc.language |
eng |
dc.publisher |
Nature Publishing Group |
dc.relation |
Versió postprint del document publicat a: https://doi.org/10.1038/sj.onc.1209648 |
dc.relation |
Oncogene, 2006, vol. 25, num. 47, p. 6304-6318 |
dc.rights |
(c) Nature Publishing Group, 2006 |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Apoptosis |
dc.subject |
Autophagy |
dc.subject |
Kinases |
dc.subject |
Indirubins |
dc.subject |
Caspases |
dc.subject |
Apoptosi |
dc.subject |
Proteïnes quinases |
dc.subject |
Càncer |
dc.subject |
Autofàgia |
dc.subject |
Mort cel·lular |
dc.subject |
Apoptosis |
dc.subject |
Protein kinases |
dc.subject |
Cancer |
dc.subject |
Autophagy |
dc.subject |
Cell death |
dc.title |
7-Bromoindirubin-3'-oxime induces caspase-independent cell death |
dc.type |
info:eu-repo/semantics/article |
dc.type |
info:eu-repo/semantics/acceptedVersion |