Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-7-13
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0167-6997
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
299-309
pubmed:dateRevised
2011-11-17
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
pubmed:year
2005
pubmed:articleTitle
A study of cytotoxic synergy of UCN-01 and flavopiridol in syngeneic pair of cell lines.
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.
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