title: Proteomic profiling identifies cyclooxygenase-2-independent global proteomic changes by celecoxib in colorectal cancer cells.
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.
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Lou
authors.forename: Naheed
authors.initials: N
authors.lastname: Fatima
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xiao
authors.forename: Stacy
authors.initials: S
authors.lastname: Stauffer
authors.forename: Gary
authors.initials: G
authors.lastname: Smythers
authors.forename: Peter
authors.initials: P
authors.lastname: Greenwald
authors.forename: Iqbal Unnisa
authors.initials: IU
authors.lastname: Ali
mesh_terms: D015153:Blotting, Western; D000068579:Celecoxib; D003110:Colonic Neoplasms / Q000737:chemistry*; D051546:Cyclooxygenase 2 / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D021984:Cyclophilin A / Q000235:genetics; D006019:Glycolysis; D045325:HCT116 Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000032:analysis*; D010544:Peroxidases / Q000235:genetics; D054464:Peroxiredoxins; D000091402:Prohibitins; D040901:Proteomics; D011720:Pyrazoles / Q000494:pharmacology*; D012097:Repressor Proteins / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D009363:Neoplasm Proteins; D000091402:Prohibitins; D011720:Pyrazoles; D012097:Repressor Proteins; D013449:Sulfonamides; D010544:Peroxidases; D054464:Peroxiredoxins; D051546:Cyclooxygenase 2; D021984:Cyclophilin A; D000068579:Celecoxib