Doxorubicin-induced death in neuroblastoma does not involve death receptors in S-type cells and is caspase-independent in N-type cells

Details

Serval ID
serval:BIB_0CCC18BD9658
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Doxorubicin-induced death in neuroblastoma does not involve death receptors in S-type cells and is caspase-independent in N-type cells
Journal
Oncogene
Author(s)
Hopkins-Donaldson  S., Yan  P., Bourloud  K. B., Muhlethaler  A., Bodmer  J. L., Gross  N.
ISSN
0950-9232
Publication state
Published
Issued date
09/2002
Peer-reviewed
Oui
Volume
21
Number
39
Pages
6132-7
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep 5
Abstract
Death induced by doxorubicin (dox) in neuroblastoma (NB) cells was originally thought to occur via the Fas pathway, however since studies suggest that caspase-8 expression is silenced in most high stage NB tumors, it is more probable that dox-induced death occurs via a different mechanism. Caspase-8 silenced N-type invasive NB cell lines LAN-1 and IMR-32 were investigated for their sensitivity to dox, and compared to S-type noninvasive SH-EP NB cells expressing caspase-8. All cell lines had similar sensitivities to dox, independently of caspase-8 expression. Dox induced caspase-3, -7, -8 and -9 and Bid cleavage in S-type cells and death was blocked by caspase inhibitors but not by oxygen radical scavenger BHA. In contrast, dox-induced death in N-type cells was caspase-independent and was inhibited by BHA. Dox induced a drop in mitochondrial membrane permeability in all cell lines. Dox-induced death in S-type cells gave rise to apoptotic nuclei, whereas in N-type cells nuclei were non-apoptotic in morphology. Transfection of SH-EP cells with a dominant negative FADD mutant inhibited TRAIL-induced death, but had no effect on dox-induced apoptosis. These results suggest that S-type cells undergo apoptosis after dox treatment independently of death receptors, whereas N-type cells are killed by a caspase-independent mechanism.
Keywords
*Adaptor Proteins, Signal Transducing Antineoplastic Agents/*pharmacology Antioxidants/pharmacology Apoptosis/*drug effects/physiology Apoptosis Regulatory Proteins Butylated Hydroxyanisole/pharmacology Carrier Proteins/genetics/immunology/*metabolism Caspases/antagonists & inhibitors/*metabolism Cell Nucleus/metabolism Cell Survival/drug effects/physiology Cells, Cultured Doxorubicin/*pharmacology Drug Resistance, Neoplasm/physiology Enzyme Inhibitors/pharmacology Fas-Associated Death Domain Protein Genes, Dominant Humans Membrane Glycoproteins/pharmacology Neoplasm Invasiveness/physiopathology Neuroblastoma/*drug therapy/*metabolism/pathology Reactive Oxygen Species TNF-Related Apoptosis-Inducing Ligand Transfection Tumor Necrosis Factor-alpha/pharmacology Tumor Suppressor Protein p53/genetics/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
20/01/2008 16:55
Last modification date
20/08/2019 13:34
Usage data