Celecoxib can induce cell death independently of cyclooxygenase-2, p53, Mdm2, c-Abl and reactive oxygen species
Related Experiment Video
Updated: Aug 6, 2026
A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions
Published on: May 27, 2021
Sue Haupt1, Jackie Kleinstern, Ygal Haupt
1Department 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.
Insights
Celecoxib resistance in cells lacking cyclooxygenase-2 (COX-2) was observed. Despite inducing reactive oxygen species (ROS), celecoxib
Area of Science:
- Pharmacology
- Cell Biology
- Biochemistry
Background:
- Cyclooxygenase-2 (COX-2) is a target for celecoxib.
- Some cell lines exhibit resistance to celecoxib at normal plasma concentrations.
Purpose of the Study:
- To investigate the mechanisms of celecoxib resistance and cell death.
- To explore the role of p53, Hdm2, and reactive oxygen species (ROS) in celecoxib's effects.
Main Methods:
- Exposure of cell lines to varying concentrations of celecoxib.
- Assessment of cell growth inhibition and death.
- Analysis of p53 and Hdm2 protein levels.
- Measurement of reactive oxygen species (ROS) generation.
- In vitro xanthine oxidase activity assay.
Main Results:
- Cell lines lacking functional COX-2 were resistant to celecoxib.
- Celecoxib inhibited cell growth at 80 µmol/l and induced death at 120 µmol/l.
- Cell death and growth inhibition were independent of p53 and Hdm2.
- Celecoxib induced ROS generation within 4 hours, independent of p53 and c-Abl.
- In vitro, celecoxib enhanced superoxide radical production by xanthine oxidase.
- Antioxidants failed to protect cells from celecoxib-induced death.
Conclusions:
- Celecoxib resistance is linked to the absence of functional COX-2.
- Celecoxib induces cell death through a mechanism independent of ROS, despite ROS generation.
- p53 and Hdm2 are not essential mediators of celecoxib-induced cell death in these models.
Related Concept Videos
01:31The Intrinsic Apoptotic Pathway
02:23Abnormal Proliferation
01:30Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
01:17The Extrinsic Apoptotic Pathway
02:34Inhibition of Cdk Activity
01:23Negative Regulator Molecules