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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2002-3-25
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pubmed:abstractText |
Flavopiridol is a potent inhibitor of cyclin-dependent kinases (cdks). In a large proportion of solid tumor cell lines, the initial response to flavopiridol is cell cycle arrest. NCI-H661 non-small cell lung cancer cells are representative of a subset of more sensitive cell lines in which apoptosis is observed during the first 24 h of drug exposure. Analysis of the apoptotic population indicates that cells in S-phase are preferentially dying. In addition, cells are sensitized to flavopiridol following recruitment to S-phase, whether accomplished by synchronization or by treatment with noncytotoxic concentrations of chemotherapy agents that impose an S-phase delay. Combinations of gemcitabine or cisplatin, followed by flavopiridol at concentrations that correlate with cdk inhibition, produce sequence-dependent cytotoxic synergy. A survey of paired cell lines, including WI38 diploid fibroblasts or normal human bronchial epithelial cells, along with their SV40-transformed counterparts, demonstrates that treatment with flavopiridol during S-phase is selectively cytotoxic to transformed cells. These data suggest that treatment during S-phase may maximize responses to flavopiridol and that the administration of flavopiridol after chemotherapy agents that cause S-phase accumulation may be an efficacious antitumor strategy.
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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/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cisplatin,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxycytidine,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids,
http://linkedlifedata.com/resource/pubmed/chemical/Piperidines,
http://linkedlifedata.com/resource/pubmed/chemical/flavopiridol,
http://linkedlifedata.com/resource/pubmed/chemical/gemcitabine
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0008-5472
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
62
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1707-17
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11912144-Antineoplastic Agents,
pubmed-meshheading:11912144-Antineoplastic Combined Chemotherapy Protocols,
pubmed-meshheading:11912144-Apoptosis,
pubmed-meshheading:11912144-Bronchi,
pubmed-meshheading:11912144-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:11912144-Cell Cycle,
pubmed-meshheading:11912144-Cell Line, Transformed,
pubmed-meshheading:11912144-Cisplatin,
pubmed-meshheading:11912144-Cyclin-Dependent Kinases,
pubmed-meshheading:11912144-DNA,
pubmed-meshheading:11912144-DNA, Neoplasm,
pubmed-meshheading:11912144-Deoxycytidine,
pubmed-meshheading:11912144-Drug Interactions,
pubmed-meshheading:11912144-Enzyme Inhibitors,
pubmed-meshheading:11912144-Epithelial Cells,
pubmed-meshheading:11912144-Fibroblasts,
pubmed-meshheading:11912144-Flavonoids,
pubmed-meshheading:11912144-Humans,
pubmed-meshheading:11912144-Lung Neoplasms,
pubmed-meshheading:11912144-Piperidines,
pubmed-meshheading:11912144-S Phase,
pubmed-meshheading:11912144-Tumor Cells, Cultured
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pubmed:year |
2002
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pubmed:articleTitle |
Selective sensitization of transformed cells to flavopiridol-induced apoptosis following recruitment to S-phase.
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pubmed:affiliation |
Department of Adult Oncology and Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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