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Open Access Green as soon as Postprint is submitted to ZB.
Spongistatin 1: A new chemosensitizing marine compound that degrades XIAP.
Leukemia 22, 1737-1745 (2008)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
apoptosis; spongistatin 1; XIAP; chemoresistance; chemosensitization
ISSN (print) / ISBN
0887-6924
e-ISSN
1476-5551
Journal
Leukemia
Quellenangaben
Volume: 22,
Issue: 9,
Pages: 1737-1745
Publisher
Nature Publishing Group
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Research Unit Gene Vector (AGV)