Source:http://linkedlifedata.com/resource/pubmed/id/17013758
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
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| pubmed:dateCreated |
2006-11-6
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| pubmed:abstractText |
Aberrant apoptosis has been associated with the development and therapeutic resistance of cancer. Recent studies suggest that caspase deficiency/downregulation is frequently detected in different cancers. We have previously shown that caspase-3 reconstitution significantly sensitized MCF-7 cells to doxorubicin and etoposide. In contrast to the well established role of caspase-3 as an effector caspase, the focus of this study is to delineate caspase-3 induced feedback activation of the apical caspases-2, -8, -9 and -10A in doxorubicin and TNF-alpha induced apoptosis. Using cell-free systems we show that caspases-9 and 2 are the most sensitive, caspase-8 is less sensitive and caspase-10A is the least sensitive to caspase-3 mediated-cleavage. When apoptosis is induced by doxorubicin or TNF-alpha in an intact cell model, cleavage of caspases-8 and -9, but not caspase-2, was markedly enhanced by caspase-3. Caspase-3 mediated-feedback and activation of caspase-8 and -9 in MCF-7/C3 cells is further supported by an increase in the cleavage of caspase-8 and 9 substrates and cytochrome c release. These data indicate that, in addition to its function as an effector caspase, caspase-3 plays an important role in maximizing the activation of apical caspases and crosstalk between the two major apoptotic pathways. The significant impact of caspase-3 on both effector and apical caspases suggests that modulation of caspase-3 activity would be a useful approach to overcome drug resistance in clinical oncology.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibiotics, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/CASP10 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 10,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Doxorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
1360-8185
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
11
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1987-97
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| pubmed:meshHeading |
pubmed-meshheading:17013758-Antibiotics, Antineoplastic,
pubmed-meshheading:17013758-Apoptosis,
pubmed-meshheading:17013758-Caspase 10,
pubmed-meshheading:17013758-Caspase 2,
pubmed-meshheading:17013758-Caspase 3,
pubmed-meshheading:17013758-Caspase 8,
pubmed-meshheading:17013758-Caspase 9,
pubmed-meshheading:17013758-Cell Line, Tumor,
pubmed-meshheading:17013758-Cysteine Endopeptidases,
pubmed-meshheading:17013758-Cytosol,
pubmed-meshheading:17013758-Doxorubicin,
pubmed-meshheading:17013758-Humans,
pubmed-meshheading:17013758-Tumor Necrosis Factor-alpha
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| pubmed:year |
2006
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| pubmed:articleTitle |
Caspase-3 mediated feedback activation of apical caspases in doxorubicin and TNF-alpha induced apoptosis.
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| pubmed:affiliation |
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.
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