Academic Journal
Drug-mediated sensitization to TRAIL-induced apoptosis in caspase-8-complemented neuroblastoma cells proceeds via activation of intrinsic and extrinsic pathways and caspase-dependent cleavage of XIAP, Bcl-xL and RIP
| العنوان: | Drug-mediated sensitization to TRAIL-induced apoptosis in caspase-8-complemented neuroblastoma cells proceeds via activation of intrinsic and extrinsic pathways and caspase-dependent cleavage of XIAP, Bcl-xL and RIP |
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| المؤلفون: | Muhlethaler-Mottet, A., Bourloud, K. B., Auderset, K., Joseph, J. M., Gross, N. |
| المصدر: | Oncogene, vol. 23, no. 32, pp. 5415-25 |
| سنة النشر: | 2004 |
| المجموعة: | Université de Lausanne (UNIL): Serval - Serveur académique lausannois |
| مصطلحات موضوعية: | Antineoplastic Agents/*pharmacology Apoptosis/*drug effects Apoptosis Regulatory Proteins Caspase 8 Caspases/*metabolism Cycloheximide/pharmacology Humans Membrane Glycoproteins/*pharmacology Mitochondria/drug effects Neuroblastoma/*drug therapy/metabolism/pathology Protein Synthesis Inhibitors/pharmacology Proteins/metabolism Proto-Oncogene Proteins c-bcl-2/metabolism Receptor-Interacting Protein Serine-Threonine Kinases Receptors, TNF-Related Apoptosis-Inducing Ligand Receptors, Tumor Necrosis Factor/biosynthesis/drug effects/genetics TNF-Related Apoptosis-Inducing Ligand Tumor Cells, Cultured Tumor Necrosis Factor-alpha/*pharmacology X-Linked Inhibitor of Apoptosis Protein bcl-X Protein |
| الوصف: | Neuroblastoma (NB) is a childhood neoplasm which heterogeneous behavior can be explained by differential regulation of apoptosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces rapid apoptosis in most tumor cells and thus represents a promising anticancer agent. We have reported silencing of caspase-8 expression in highly malignant NB cells as a possible mechanism of resistance to TRAIL-induced apoptosis. To explore the particular contribution of caspase-8 in such resistance, retroviral-mediated stable caspase-8 expression was induced in the IGR-N91 cells. As a result, sensitivity to TRAIL was fully restored in the caspase-8-complemented cells. TRAIL-induced cell death could be further enhanced by cotreatment of IGR-N91-C8 and SH-EP cells with cycloheximide or subtoxic concentrations of chemotherapeutic drugs in a caspase-dependent manner. Sensitization to TRAIL involved enhanced death receptor DR5 expression, activation of Bid and the complete caspases cascade. Interestingly, combined treatments also enhanced the cleavage-mediated inactivation of antiapoptotic molecules, XIAP, Bcl-x(L) and RIP.Our results show that restoration of active caspase-8 expression in a caspase-8-deficient NB cell line is necessary and sufficient to fully restore TRAIL sensitivity. Moreover, the synergistic effect of drugs and TRAIL results from activation of the caspase cascade via a mitochondrial pathway-mediated amplification loop and from the inactivation of apoptosis inhibitors. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/15094781; info:eu-repo/semantics/altIdentifier/pissn/0950-9232; https://serval.unil.ch/notice/serval:BIB_FCF0DF607D2F |
| DOI: | 10.1038/sj.onc.1207704 |
| الاتاحة: | https://serval.unil.ch/notice/serval:BIB_FCF0DF607D2F https://doi.org/10.1038/sj.onc.1207704 |
| رقم الانضمام: | edsbas.3D4E8F4B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/sj.onc.1207704 |
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