The C-terminal CD47/IAP-binding domain of thrombospondin-1 prevents camptothecin- and doxorubicin-induced apoptosis in human thyroid carcinoma cells.

Rath, Géraldine;Schneider, C.;Dedieu, S.;Rothhut, B.;Martiny, L.;et.al.
(2006) Biochimica et Biophysica Acta : international journal of biochemistry and biophysics — Vol. 1763, n° 10, p. 1125-1134 (2006)

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Authors
  • Rath, GéraldineUniversité de Reims Champagne Ardennes
    Author
  • Schneider, C.
    Author
  • Dedieu, S.
    Author
  • Rothhut, B.
    Author
  • Sid, BriceUCLouvain
    Author
  • Martiny, L.
    Author
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Abstract
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.
Affiliations
  • Université de Reims Champagne ArdennesUMR CNRS 6198

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Rath, G., Schneider, C., Dedieu, S., Rothhut, B., Soula-Rothhut, M., Ghoneim, C., Sid, B., Morjani, H., El Btaouri, H., & Martiny, L. (2006). The C-terminal CD47/IAP-binding domain of thrombospondin-1 prevents camptothecin- and doxorubicin-induced apoptosis in human thyroid carcinoma cells. Biochimica et Biophysica Acta : international journal of biochemistry and biophysics, 1763(10), 1125-1134. https://doi.org/10.1016/j.bbamcr.2006.08.001 (Original work published 2006)