Restoration of TRAIL-induced apoptosis in a caspase-8-deficient neuroblastoma cell line by stable re-expression of caspase-8
Details
Serval ID
serval:BIB_FDA23CBEABBA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Restoration of TRAIL-induced apoptosis in a caspase-8-deficient neuroblastoma cell line by stable re-expression of caspase-8
Journal
Annals of the New York Academy of Sciences
ISSN
0077-8923 (Print)
Publication state
Published
Issued date
12/2003
Volume
1010
Pages
195-9
Notes
Journal Article --- Old month value: Dec
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in most tumor cells, a process sometimes potentiated by chemotherapeutic drugs or cycloheximide (CHX). Childhood neuroblastoma (NB) is a clinically and biologically heterogeneous neoplasm whose behavior can be explained by differential regulation of apoptosis. The non-invasive S-type NB cell lines are sensitive to TRAIL, whereas the invasive N-type NB cell lines are resistant. We have reported the silencing of caspase-8 expression in N-type cells as a possible mechanism of death receptor-mediated resistance to apoptosis in NB. The recently observed deregulation of caspase-10 in these cells prompted us to investigate the particular contribution of caspase-8 silencing in the resistance to TRAIL in N-type cells. Stable caspase-8 expression was therefore restored in the IGR-N91 cell line by retroviral infection. The IGR-N91-C8 cells became sensitive to TRAIL-mediated apoptosis, whereas the control vector-infected IGR-N91-M cells remained resistant. Interestingly, the apoptotic response to TRAIL was enhanced by co-treatment of SH-EP and IGR-N91-C8 cells with CHX or with sub-toxic concentration of doxorubicin (DOX) in a caspase-dependent manner, as cells could be protected from death by specific caspase-8 or pan-caspase inhibitors. CHX or DOX was shown to enhance TRAIL-induced caspase-8 activation and loss of mitochondrial transmembrane potential. In conclusion, restoration of active caspase-8 expression in caspase-8- and caspase-10-deficient IGR-N-91 cell line is necessary and sufficient to fully restore TRAIL-mediated cell death. Moreover, DOX and CHX were able to sensitize NB cell lines to TRAIL-induced apoptosis in a caspase-8-dependent manner by engaging death receptor and mitochondrial signaling pathways.
Keywords
Animals
Apoptosis/genetics/*physiology
Apoptosis Regulatory Proteins
Caspase 8
Caspases/deficiency/*genetics/*metabolism
Cell Death/physiology
Cell Line, Tumor
Cycloheximide/pharmacology
DNA Damage
Enzyme Activation/drug effects
Gene Expression Regulation, Neoplastic
Humans
Membrane Glycoproteins/*physiology
Neuroblastoma
TNF-Related Apoptosis-Inducing Ligand
Tumor Necrosis Factor-alpha/*physiology
Pubmed
Web of science
Create date
28/01/2008 10:07
Last modification date
20/08/2019 17:28