Linked Life Data

11313863

Source:http://linkedlifedata.com/resource/pubmed/id/11313863

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2001-4-23
pubmed:abstractText
Apoptosis can be induced by various stimuli including DNA-damaging anticancer drugs and the protein kinase inhibitor staurosporine. It is generally believed that the molecular events during execution of apoptosis are shared, as both anticancer drugs and staurosporine derivatives induce mitochondrial damage, cytochrome c release and the activation of the caspase-9 proteolytic cascade. In the present study we show that overexpression of a dominant-negative caspase-9 mutant abolished the activation of endogenous caspase-9, caspase-3 and the cleavage of the caspase substrate Bid in response to anticancer drug treatment. Surprisingly, however, only marginal effects were observed during staurosporine-induced apoptosis. Furthermore, we describe a Jurkat T-cell clone that is completely resistant towards different anticancer drugs, but remains sensitive towards staurosporine-induced apoptosis. In these cells only staurosporine, but neither anti-CD95 nor anticancer drugs were able to trigger caspase activity and the cleavage of caspase substrates. Our results therefore suggest that the mechanism of staurosporine-induced apoptosis is more complex and at least partially differs from anticancer drug-induced caspase activation. These distinct features of staurosporine may allow to bypass chemoresistance of tumor cells and may encourage further clinical trials for the use of staurosporine derivatives in antitumor therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1193-202
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Staurosporine and conventional anticancer drugs induce overlapping, yet distinct pathways of apoptosis and caspase activation.
pubmed:affiliation
Department of Immunology and Cell Biology, University of Münster, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't