Document Detail


The C-terminal CD47/IAP-binding domain of thrombospondin-1 prevents camptothecin- and doxorubicin-induced apoptosis in human thyroid carcinoma cells.
MedLine Citation:
PMID:  16962673     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Camptothecin and doxorubicin belong to a family of anticancer drugs that exert cytotoxic effects by triggering apoptosis in various cell types. However there have only been few investigations showing that matricellular proteins like thrombospondin-1 (TSP-1) could be involved in the underlying mechanism of this cytotoxicity. In this report, using Hoechst reagent staining, reactive oxygen species production and caspase-3 activity measurement, we determined that both camptothecin and doxorubicin induced apoptosis in human thyroid carcinoma cells (FTC-133). On the one hand, we demonstrated that camptothecin and doxorubicin inhibited TSP-1 expression mainly occurring at the transcriptional level. On the other hand, drug-induced apoptosis determined by western blot analysis for PARP cleavage and caspase-3 activity measurement, was significantly decreased in presence of exogenous TSP-1. In order to identify the sequence responsible for this effect, we used the CD47/IAP-binding peptide 4N1 (RFYVVMWK), derived from the C-terminal domain of TSP-1, and known to play a role in apoptosis. Thus, in presence of 4N1, camptothecin and doxorubicin-induced pro-apoptotic activity was considerably inhibited. These findings suggest that induction of apoptosis by camptothecin or doxorubicin in FTC-133 cells is greatly dependent by a down-regulation of TSP-1 expression and shed new light on a possible role for TSP-1 in drug resistance.
Authors:
G M Rath; C Schneider; S Dedieu; B Rothhut; M Soula-Rothhut; C Ghoneim; B Sid; H Morjani; H El Btaouri; L Martiny
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-08-05
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1763     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-10-03     Completed Date:  2006-12-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1125-34     Citation Subset:  IM    
Affiliation:
Université de Reims Champagne-Ardenne, IFR 53 Biomolécules, UMR-CNRS 6198 Matrice extracellulaire et régulation cellulaire, UFR Sciences de Reims, Moulin de la Housse-BP 1039-51687 Reims Cedex 2, France. geraldine.rath@univ-reims.fr
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD47 / genetics,  metabolism*
Apoptosis
Binding Sites
Camptothecin / pharmacology*
Carcinoma / metabolism*,  pathology
Cell Differentiation
Cell Line, Tumor
Doxorubicin / pharmacology*
Humans
Thrombospondin 1 / genetics,  metabolism*
Thyroid Neoplasms / metabolism*,  pathology
Time Factors
Transfection
Chemical
Reg. No./Substance:
0/Antigens, CD47; 0/Thrombospondin 1; 23214-92-8/Doxorubicin; 7689-03-4/Camptothecin

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