| The C-terminal CD47/IAP-binding domain of thrombospondin-1 prevents camptothecin- and doxorubicin-induced apoptosis in human thyroid carcinoma cells. | |
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MedLine Citation:
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PMID: 16962673 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-08-05 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1763 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2006 Oct |
Date Detail:
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Created Date: 2006-10-03 Completed Date: 2006-12-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1125-34 Citation Subset: IM |
Affiliation:
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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:
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Antigens, CD47
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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:
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0/Antigens, CD47; 0/Thrombospondin 1; 23214-92-8/Doxorubicin; 7689-03-4/Camptothecin |
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