Proteomic Profiling Identifies Cyclooxygenase-2-Independent Global Proteomic Changes by Celecoxib in Colorectal Cancer Cells

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 15; no. 9; pp. 1598 - 1606
• Main Authors: Lou, Jianrong, Fatima, Naheed, Xiao, Zhen, Stauffer, Stacy, Smythers, Gary, Greenwald, Peter, Ali, Iqbal Unnisa
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.09.2006
• Subjects: Antineoplastic agents; Biological and medical sciences; Blotting, Western; Celecoxib; Colonic Neoplasms - chemistry; Colorectal cancer; COX-2; Cyclooxygenase 2 - physiology; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclophilin A - genetics; General aspects; Glycolysis; HCT116 Cells; Humans; Medical sciences; Neoplasm Proteins - analysis; Peroxidases - genetics; Peroxiredoxins; Pharmacology. Drug treatments; Proteomics; Pyrazoles - pharmacology; Repressor Proteins - genetics; Sulfonamides - pharmacology; Tumors; Two-dimensional DIGE; Antineoplastic agent; Human; Prostaglandin-endoperoxide synthase; Rectal disease; Enzyme; Cyclooxygenase 2; Colorectal cancer; Enzyme inhibitor; Biological marker; Cyclooxygenase 2 inhibitor; Celecoxib; Colonic disease; Non steroidal antiinflammatory agent; Cancerology; Established cell line; Proteomics; Digestive diseases; Intestinal disease; Oxidoreductases
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-06-0216

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. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1598–606)