7-Bromoindirubin-3′-oxime induces caspase-independent cell death
| Autor: | Jacint Boix, Karima Bettayeb, Frank Totzke, Alexios-Leandros Skaltsounis, Jan Mester, Xènia Garrofé-Ochoa, Laurent Meijer, Panos Polychronopoulos, Yoan Ferandin, Prokopios Magiatis, Judit Ribas, Marie Knockaert, Christoph Schächtele |
|---|---|
| Přispěvatelé: | Departament de Quimica Inorgànica, Facultat de Quimica, Universitat de Barcelona (UB), Molécules et cibles thérapeutiques (MCT), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2006 |
| Předmět: |
Male
Swine MESH: Cell Cycle Apoptosis Glycogen Synthase Kinase 3 Mice Starfish MESH: Structure-Activity Relationship 0302 clinical medicine Oximes MESH: Protein Kinase Inhibitors MESH: Animals MESH: Tumor Suppressor Protein p53 Càncer MESH: Swine MESH: Glycogen Synthase Kinase 3 Cancer MESH: Indoles 0303 health sciences MESH: Starfish Cell Cycle MESH: STAT3 Transcription Factor MESH: Oximes MESH: CDC2 Protein Kinase Cyclin-Dependent Kinases 3. Good health Cell biology Cell Death Process Caspases 030220 oncology & carcinogenesis MESH: Cell Nucleus Cyclin-Dependent Kinase Inhibitor p21 Recombinant Fusion Proteins bcl-X Protein Cysteine Proteinase Inhibitors Spodoptera MESH: Cyclin-Dependent Kinase Inhibitor p21 Structure-Activity Relationship 03 medical and health sciences MESH: Recombinant Fusion Proteins Genetics Humans Molecular Biology MESH: Humans MESH: Caspases MESH: Phosphorylation MESH: Amino Acid Chloromethyl Ketones Apoptosi Aryl hydrocarbon receptor MESH: Cell Line Proteïnes quinases MESH: Proto-Oncogene Proteins c-bcl-2 chemistry Indirubin MESH: Female MESH: Cell Death Cancer Research Indoles Amino Acid Chloromethyl Ketones chemistry.chemical_compound Protein kinases Phosphorylation Caspase MESH: Spodoptera Cell Death biology MESH: Cyclin-Dependent Kinases Proto-Oncogene Proteins c-bcl-2 Biochemistry Mort cel·lular Quinolines Female Indirubins MESH: Quinolines STAT3 Transcription Factor Cell death Programmed cell death MESH: Cell Line Tumor Necroptosis Kinases MESH: bcl-X Protein Cell Line MESH: Cysteine Proteinase Inhibitors Autofàgia Cyclin-dependent kinase Cell Line Tumor CDC2 Protein Kinase Autophagy Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Mice Protein Kinase Inhibitors 030304 developmental biology Cell Nucleus MESH: Male MESH: Protein Processing Post-Translational biology.protein Tumor Suppressor Protein p53 Protein Processing Post-Translational |
| Zdroj: | Repositorio Abierto de la UdL Universitad de Lleida Oncogene Oncogene, Nature Publishing Group, 2006, 25 (47), pp.6304-18. ⟨10.1038/sj.onc.1209648⟩ Recercat. Dipósit de la Recerca de Catalunya instname Oncogene, 2006, 25 (47), pp.6304-18. ⟨10.1038/sj.onc.1209648⟩ |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|