|LY294002, an inhibitor of PI-3K, enhances heat sensitivity independently of p53 status in human lung cancer cells.|
|PMID: 16773206 Owner: NLM Status: MEDLINE|
|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.|
|Ken Ohnishi; Jun-Ichi Yasumoto; Akihisa Takahashi; Takeo Ohnishi|
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|Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't|
|Title: International journal of oncology Volume: 29 ISSN: 1019-6439 ISO Abbreviation: Int. J. Oncol. Publication Date: 2006 Jul|
|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|
|Languages: eng Pagination: 249-53 Citation Subset: IM|
|Department of Biology, Nara Medical University School of Medicine, Kashihara, Nara 634-8521, Japan.|
|APA/MLA Format Download EndNote Download BibTex|
antagonists & inhibitors*,
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
Lung Neoplasms / enzymology*, genetics, therapy
Microtubule-Associated Proteins / metabolism
Morpholines / pharmacology*
Neoplasm Proteins / metabolism
Phosphorylation / drug effects
Protein Kinase Inhibitors / pharmacology*
Proto-Oncogene Proteins c-akt / metabolism
Response Elements / genetics
Transcription Factors / metabolism
Tumor Stem Cell Assay
Tumor Suppressor Protein p53 / genetics, metabolism*
Up-Regulation / drug effects
|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 188.8.131.52/1-Phosphatidylinositol 3-Kinase; EC 184.108.40.206/Proto-Oncogene Proteins c-akt|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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