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Anticancer Drugs. 2006 Jul;17(6):609-19.

Celecoxib can induce cell death independently of cyclooxygenase-2, p53, Mdm2, c-Abl and reactive oxygen species.

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1
Department of Hematology, Hadassah University Hospital, Jerusalem, Israel. haupt@vms.huji.ac.il

Abstract

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.

[Indexed for MEDLINE]

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