Abstract:
:Spongistatin 1, a marine experimental substance with chemotherapeutic potential, induces apoptosis and inhibits clonogenic survival of MCF-7 cells. Regarding the apoptotic signaling pathways of spongistatin 1, we present two major facts. Firstly, spongistatin 1-induced cell death, mainly caspase-independent, involves the proapoptotic proteins apoptosis-inducing factor and endonuclease G. Both proteins translocate from mitochondria to the nucleus and contribute to spongistatin 1-mediated apoptosis as shown via gene silencing. Secondly, spongistatin 1 acts as a tubulin depolymerizing agent and is able to free the proapoptotic Bcl-2 family member Bim from its sequestration both by the microtubular complex and by the antiapoptotic protein Mcl-1. Silencing of Bim by small interfering RNA leads to a diminished translocation of apoptosis-inducing factor and endonuclease G to the nucleus and subsequently reduces apoptosis rate. Thus, we identified Bim as an important factor upstream of mitochondria executing a central role in the caspase-independent apoptotic signaling pathway induced by spongistatin 1. Taken together, spongistatin 1 is both a valuable tool for the characterization of apoptotic pathways and a promising experimental anticancer drug.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Schneiders UM,Schyschka L,Rudy A,Vollmar AMdoi
10.1158/1535-7163.MCT-08-1179subject
Has Abstractpub_date
2009-10-01 00:00:00pages
2914-25issue
10eissn
1535-7163issn
1538-8514pii
1535-7163.MCT-08-1179journal_volume
8pub_type
杂志文章abstract::DNA topoisomerase I (Top1) inhibition by camptothecin derivatives can impair the hypoxia-induced cell transcriptional response. In the present work, we determined molecular aspects of the mechanism of camptothecin's effects on hypoxia-inducible factor-1α (HIF-1α) activity in human cancer cells. In particular, we provi...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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更新日期:2014-11-01 00:00:00
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-11-0182
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pub_type: 杂志文章
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更新日期:2010-08-01 00:00:00
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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更新日期:2010-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-05-0236
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
更新日期:2004-02-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章,多中心研究
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更新日期:2016-03-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-07-2409
更新日期:2008-07-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0581
更新日期:2007-03-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章,评审
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更新日期:2011-09-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0691
更新日期:2007-03-01 00:00:00
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pub_type: 杂志文章
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更新日期:2011-12-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type:
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更新日期:2010-01-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-0534
更新日期:2009-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:2017-12-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0315
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pub_type: 杂志文章
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更新日期:2008-10-01 00:00:00