Spongistatin 1: A new chemosensitizing marine compound that degrades XIAP

L. Schyschka, A. Rudy, I. Jeremias, N. Barth, George Pettit, A. M. Vollmar

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Spongistatin 1 is a new experimental chemotherapeutic agent isolated from marine sponges. Here we show that spongistatin 1 potently induces cell death in patient primary acute leukemic cells with higher efficiency than 8/10 clinically used cytotoxic drugs and prevents long-term survival of leukemic cell lines. Spongistatin 1 triggers caspase-dependent apoptosis in Jurkat T cells by the release of cytochrome c, Smac/DIABLO and Omi/HtrA2. As caspase-9 acts as an initiator caspase and Bcl-2 and Bcl-xL overexpression suppress spongistatin 1-induced apoptosis, cell death is mediated through the mitochondrial apoptosis pathway. Importantly, spongistatin 1 leads to the degradation of the antiapoptotic X-linked inhibitor of apoptosis protein. In apoptosis-resistant leukemic tumor cells overexpressing XIAP, spongistatin 1 effectively causes cell death and potentiates cell death induction by other apoptosis-promoting factors that might be caused by spongistatin 1-mediated degradation of XIAP. Our data show that spongistatin 1 represents a promising novel therapeutic agent for the treatment of leukemic tumor cells especially in the clinically highly relevant situation of chemoresistance due to overexpression of XIAP.

Original languageEnglish (US)
Pages (from-to)1737-1745
Number of pages9
JournalLeukemia
Volume22
Issue number9
DOIs
StatePublished - 2008

Fingerprint

Apoptosis
Cell Death
Initiator Caspases
X-Linked Inhibitor of Apoptosis Protein
Caspase 2
Jurkat Cells
spongistatin 1
Caspase 9
Porifera
Caspases
Cytochromes c
Cause of Death
Neoplasms
T-Lymphocytes
Cell Line
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Schyschka, L., Rudy, A., Jeremias, I., Barth, N., Pettit, G., & Vollmar, A. M. (2008). Spongistatin 1: A new chemosensitizing marine compound that degrades XIAP. Leukemia, 22(9), 1737-1745. https://doi.org/10.1038/leu.2008.146

Spongistatin 1 : A new chemosensitizing marine compound that degrades XIAP. / Schyschka, L.; Rudy, A.; Jeremias, I.; Barth, N.; Pettit, George; Vollmar, A. M.

In: Leukemia, Vol. 22, No. 9, 2008, p. 1737-1745.

Research output: Contribution to journalArticle

Schyschka, L, Rudy, A, Jeremias, I, Barth, N, Pettit, G & Vollmar, AM 2008, 'Spongistatin 1: A new chemosensitizing marine compound that degrades XIAP', Leukemia, vol. 22, no. 9, pp. 1737-1745. https://doi.org/10.1038/leu.2008.146
Schyschka, L. ; Rudy, A. ; Jeremias, I. ; Barth, N. ; Pettit, George ; Vollmar, A. M. / Spongistatin 1 : A new chemosensitizing marine compound that degrades XIAP. In: Leukemia. 2008 ; Vol. 22, No. 9. pp. 1737-1745.
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