Source:http://linkedlifedata.com/resource/pubmed/id/11905052
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2002-3-21
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pubmed:abstractText |
We have previously reported that cisplatin induces caspase-9 activation in head and neck squamous cell carcinoma cells (HNSCCs) in vitro, and the use of a specific inhibitor of caspase-9 blocks cisplatin-induced apoptosis in HNSCCs. Our purpose here was to determine whether HNSCCs selected for resistance to cisplatin fail to exhibit caspase-9 activation in response to cisplatin. Cisplatin-resistant HNSCCs (CRHNSCCs) were selected for growth in the presence of cisplatin. Following cisplatin treatment, no protelyzed caspase-9 subunits were detected in the CRHNSCCs, whereas proteolytic degradation of procaspase-9 was observed in parental cisplatin-sensitive HNSCCs (CSHNSCCs). Using a direct enzymatic assay measuring cleavage of the synthetic peptide substrate (LEHD-AFC), caspase-9 activity in cisplatin-treated CRHNSCCs was less than that in cisplatin-treated CSHNSCCs. Because caspase-9 activation requires the release of mitochondorial cytochrome c (Cyt c) into the cytoplasm, we determined the level of cytoplasmic Cyt c in response to cisplatin treatment. Interestingly, following cisplatin treatment, the same extent of increase in cytoplasmic Cyt c was evident and the expression of Bcl-2 family proteins (Bcl-2 and Bcl-XL) remained unchanged in both CRHNSCCs and CSHNSCCs. These results suggest that in certain HNSCC cell types, inhibition of caspase-9 activity represents another mechanism of acquired cisplatin resistance. This inhibition mechanism may be independent of the release of Cyt c into the cytoplasm.
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pubmed:language |
jpn
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/CASP9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cisplatin,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome c Group
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0030-6622
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
105
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
152-7
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pubmed:dateRevised |
2011-7-28
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pubmed:meshHeading |
pubmed-meshheading:11905052-Antineoplastic Agents,
pubmed-meshheading:11905052-Apoptosis,
pubmed-meshheading:11905052-Carcinoma, Squamous Cell,
pubmed-meshheading:11905052-Caspase 9,
pubmed-meshheading:11905052-Caspases,
pubmed-meshheading:11905052-Cisplatin,
pubmed-meshheading:11905052-Cytochrome c Group,
pubmed-meshheading:11905052-Drug Resistance, Neoplasm,
pubmed-meshheading:11905052-Head and Neck Neoplasms,
pubmed-meshheading:11905052-Humans,
pubmed-meshheading:11905052-Tumor Cells, Cultured
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pubmed:year |
2002
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pubmed:articleTitle |
[Inhibition of caspase-9 activity in cisplatin-resistant head and neck squamous cell carcinoma].
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pubmed:affiliation |
Department of Otolaryngology, St. Marianna University School of Medicine, Kawasaki.
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pubmed:publicationType |
Journal Article,
English Abstract,
Research Support, Non-U.S. Gov't
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