| Celecoxib can induce cell death independently of cyclooxygenase-2, p53, Mdm2, c-Abl and reactive oxygen species. | |
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MedLine Citation:
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PMID: 16917206 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cell lines that do not overexpress functional cyclooxygenase-2 are resistant to the normal plasma levels of celecoxib achieved following oral ingestion. Cell growth inhibition was demonstrated after 24 h exposure to 80 micromol/l celecoxib while significant death was not detected at concentrations below 120 micromol/l following 24 h exposure. This growth inhibition and death induction was identified to be independent of p53 and Hdm2 in these cells, despite wild-type p53 stabilization and Hdm2 diminution in some lines. Cell death induced by celecoxib was preceded by the generation of reactive oxygen species within 4 h of drug exposure. The precise mechanism of elicitation of reactive oxygen species in these cells remains to be elucidated, although it was found to be independent of p53 and c-Abl, while in vitro, celecoxib enhanced superoxide radical production by xanthine oxidase. Importantly, the failure of anti-oxidants to protect from death indicates that celecoxib induces death independently of reactive oxygen species and that reactive oxygen species generation may be an insufficient trigger of death in p53-deficient cells. |
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Authors:
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Sue Haupt; Jackie Kleinstern; Ygal Haupt; Abraham Rubinstein |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Anti-cancer drugs Volume: 17 ISSN: 0959-4973 ISO Abbreviation: Anticancer Drugs Publication Date: 2006 Jul |
Date Detail:
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Created Date: 2006-08-18 Completed Date: 2007-01-19 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9100823 Medline TA: Anticancer Drugs Country: England |
Other Details:
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Languages: eng Pagination: 609-19 Citation Subset: IM |
Affiliation:
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Department of Hematology, Hadassah University Hospital, Jerusalem, Israel. haupt@vms.huji.ac.il |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenocarcinoma
/
metabolism,
pathology Animals Antioxidants / pharmacology Apoptosis / drug effects* Blotting, Western Breast Neoplasms / metabolism, pathology Cell Proliferation / drug effects Cells, Cultured / drug effects, metabolism Colorectal Neoplasms / metabolism, pathology Cyclooxygenase 2 / genetics, physiology* Cyclooxygenase Inhibitors / pharmacology* Embryo, Mammalian / cytology, drug effects, metabolism Fibroblasts / cytology, drug effects, metabolism Humans Mice Mice, Knockout Proto-Oncogene Proteins c-abl / genetics, physiology* Proto-Oncogene Proteins c-mdm2 / genetics, physiology* Pyrazoles / pharmacology* Reactive Oxygen Species / metabolism* Sulfonamides / pharmacology* Tumor Suppressor Protein p53 / genetics, physiology* |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Cyclooxygenase Inhibitors; 0/Pyrazoles; 0/Reactive Oxygen Species; 0/Sulfonamides; 0/Tumor Suppressor Protein p53; 169590-42-5/celecoxib; EC 1.14.99.1/Cyclooxygenase 2; EC 2.7.10.2/Proto-Oncogene Proteins c-abl; EC 6.3.2.19/Proto-Oncogene Proteins c-mdm2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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