Document Detail


LY294002, an inhibitor of PI-3K, enhances heat sensitivity independently of p53 status in human lung cancer cells.
MedLine Citation:
PMID:  16773206     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of this study was to ascertain whether LY294002, an inhibitor of PI-3K, enhances heat sensitivity in human cancer cells regardless of their p53 status. Colony formation assays showed that LY294002 enhanced heat sensitivity in two human lung cancer cell lines; H1299/wild-type p53 (wtp53) and H1299/mutated p53 (mp53) cells. These cell lines have identical genetic backgrounds except for their p53 status. LY294002 suppressed the heat-induced accumulation of heat shock protein 27 (hsp27) and heat shock protein 72 (hsp72) in these cell lines. Heat-induced apoptosis was observed more frequently in H1299/wtp53 cells than in H1299/mp53 cells, and was enhanced by LY294002 in both cell lines. In addition, both the heat-induced phosphorylation of Akt and the accumulation of survivin were suppressed by LY294002. These results suggest that LY294002 inhibits anti-apoptosis signaling through hsp27 and hsp72 as well as cell survival signaling through Akt and survivin. LY294002 appears to be an attractive candidate for a p53-independent heat sensitizer in hyperthermic cancer therapy.
Authors:
Ken Ohnishi; Jun-Ichi Yasumoto; Akihisa Takahashi; Takeo Ohnishi
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  29     ISSN:  1019-6439     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-06-14     Completed Date:  2007-08-03     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  249-53     Citation Subset:  IM    
Affiliation:
Department of Biology, Nara Medical University School of Medicine, Kashihara, Nara 634-8521, Japan.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / antagonists & inhibitors*,  metabolism
Apoptosis / drug effects
Cell Line, Tumor
Cell Survival / drug effects
Chromones / pharmacology*
DNA / metabolism
DNA-Binding Proteins / metabolism
HSP27 Heat-Shock Proteins
HSP72 Heat-Shock Proteins / genetics,  metabolism
Heat-Shock Proteins / metabolism
Hot Temperature*
Humans
Hyperthermia, Induced*
Lung Neoplasms / enzymology*,  genetics,  therapy
Microtubule-Associated Proteins / metabolism
Morpholines / pharmacology*
Mutation
Neoplasm Proteins / metabolism
Phosphorylation / drug effects
Protein Kinase Inhibitors / pharmacology*
Proto-Oncogene Proteins c-akt / metabolism
Response Elements / genetics
Transcription Factors / metabolism
Transfection
Tumor Stem Cell Assay
Tumor Suppressor Protein p53 / genetics,  metabolism*
Up-Regulation / drug effects
Chemical
Reg. No./Substance:
0/BIRC5 protein, human; 0/Chromones; 0/DNA-Binding Proteins; 0/HSP27 Heat-Shock Proteins; 0/HSP72 Heat-Shock Proteins; 0/HSPB1 protein, human; 0/Heat-Shock Proteins; 0/Microtubule-Associated Proteins; 0/Morpholines; 0/Neoplasm Proteins; 0/Protein Kinase Inhibitors; 0/Transcription Factors; 0/Tumor Suppressor Protein p53; 0/heat shock transcription factor; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; 9007-49-2/DNA; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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