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Published on: September 25, 2011
Proteomic profiling identifies cyclooxygenase-2-independent global proteomic changes by celecoxib in colorectal
Jianrong Lou1, Naheed Fatima, Zhen Xiao
1Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA.
Abstract:
Celecoxib, a selective inhibitor of the enzyme cyclooxygenase-2 (COX-2), has been shown to be a promising chemoprevention agent. The chemopreventive efficacy of celecoxib is believed to be a consequence of its COX-2-dependent and COX-2-independent effects on a variety of cellular processes including proliferation, apoptosis, angiogenesis, and immunosurveillance. In an attempt to identify proteomic markers modulated by celecoxib that are independent of its inhibitory effect on COX-2, the colorectal cancer cell line HCT-116, a nonexpresser of COX-2, was treated with celecoxib. We used the powerful, state-of-the-art two-dimensional difference gel electrophoresis technology coupled with mass spectrometric sequencing to compare global proteomic profiles of HCT-116 cells before and after treatment with celecoxib. Among the differentially expressed proteins identified following celecoxib treatment were proteins involved in diverse cellular functions including glycolysis, protein biosynthesis, DNA synthesis, mRNA processing, protein folding, phosphorylation, redox regulation, and molecular chaperon activities. Our study presents a comprehensive analysis of large-scale celecoxib-modulated proteomic alterations, at least some of which may be mechanistically related to the COX-2-independent chemopreventive effect of celecoxib.
Insights
Celecoxib shows chemoprevention potential through COX-2 dependent and independent pathways. This study identified proteomic changes in colorectal cancer cells, revealing potential COX-2 independent mechanisms.
Area of Science:
- Oncology
- Proteomics
- Molecular Biology
Background:
- Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor with demonstrated chemoprevention capabilities.
- Its efficacy is attributed to both COX-2 dependent and independent cellular effects, impacting proliferation, apoptosis, angiogenesis, and immunosurveillance.
Purpose of the Study:
- To identify proteomic markers modulated by celecoxib independently of its COX-2 inhibitory action.
- To investigate the COX-2 independent chemopreventive mechanisms of celecoxib.
Main Methods:
- Utilized two-dimensional difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry.
- Analyzed global proteomic profiles of HCT-116 colorectal cancer cells (a COX-2 non-expresser) before and after celecoxib treatment.
Main Results:
- Identified differentially expressed proteins involved in key cellular functions: glycolysis, protein biosynthesis, DNA synthesis, mRNA processing, protein folding, phosphorylation, redox regulation, and molecular chaperon activity.
- Demonstrated significant proteomic alterations in HCT-116 cells following celecoxib treatment.
Conclusions:
- The study provides a comprehensive proteomic analysis of celecoxib-modulated alterations.
- These findings suggest that some identified proteomic changes may be mechanistically linked to the COX-2-independent chemopreventive effects of celecoxib.
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