rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2005-7-13
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pubmed:abstractText |
Flavopiridol and UCN-01 are two novel protein kinase inhibitors with diverse cellular effects that may complement each other with regards to induction of apoptosis. HeLa cells engineered to overexpress human survivin (HeLa-S) were at least approximately 4.8-fold resistant to UCN-01 relative to proliferation observed in control HeLa cells (HeLa-V). Flavopiridol cytotoxicity as measured using the MTT assay was unaffected in HeLa-S cells when compared with HeLa-V cells. Similarly, simultaneous treatment of HeLa-V cells with flavopiridol and UCN-01 for 72 hours did not result in synergistic inhibition of proliferation; however, in HeLa-S cells, this combination resulted in synergistic inhibition of cell proliferation. Flavopiridol and UCN-01 augmented apoptosis in HeLa-S cells (as compared with HeLa-V cells) as measured by caspase-3 cellular activity assay, DNA fragmentation and PARP cleavage by western blot. In HeLa-V and -S cells, combination treatment resulted in caspase-8 cleavage. Caspase-9 was expressed in HeLa-V cells; however, there was a marked reduction of caspase-9 content in HeLa-S cells only. Combination treatment resulted in a significant reduction in survivin abundance in HeLa-S and SKBR3-UR cells, but not in their respective parental lines. The synergy of Flavopiridol and UCN-01 are selectively toxic to survivin-overexpressing cell lines and the mechanism of toxicity involves caspase-dependent cell death.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/7-hydroxystaurosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/BIRC5 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 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type XI,
http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Apoptosis Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PARP protein, Bos taurus,
http://linkedlifedata.com/resource/pubmed/chemical/Piperidines,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine,
http://linkedlifedata.com/resource/pubmed/chemical/flavopiridol
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0167-6997
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
299-309
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:16012789-Antineoplastic Agents,
pubmed-meshheading:16012789-Apoptosis,
pubmed-meshheading:16012789-Caspase 8,
pubmed-meshheading:16012789-Caspase 9,
pubmed-meshheading:16012789-Caspases,
pubmed-meshheading:16012789-Cell Survival,
pubmed-meshheading:16012789-Collagen Type XI,
pubmed-meshheading:16012789-Dose-Response Relationship, Drug,
pubmed-meshheading:16012789-Drug Synergism,
pubmed-meshheading:16012789-Flavonoids,
pubmed-meshheading:16012789-HeLa Cells,
pubmed-meshheading:16012789-Humans,
pubmed-meshheading:16012789-Inhibitor of Apoptosis Proteins,
pubmed-meshheading:16012789-Microtubule-Associated Proteins,
pubmed-meshheading:16012789-Neoplasm Proteins,
pubmed-meshheading:16012789-Piperidines,
pubmed-meshheading:16012789-Protein Kinase Inhibitors,
pubmed-meshheading:16012789-Staurosporine,
pubmed-meshheading:16012789-Transfection
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pubmed:year |
2005
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pubmed:articleTitle |
A study of cytotoxic synergy of UCN-01 and flavopiridol in syngeneic pair of cell lines.
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pubmed:affiliation |
Albert Einstein Comprehensive Cancer Center, Department of Medicine, Albert Einstein College of Medicine, Chanin 302, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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