title: Label-free global serum proteomic profiling reveals novel celecoxib-modulated proteins in familial adenomatous polyposis patients.
abstract: Celecoxib, a selective inhibitor of cyclooxygenase-2 (Cox-2), was efficacious in clinical prevention trials of patients with familial adenomatous polyposis (FAP) and sporadic colorectal cancer. To identify as yet poorly defined molecular determinants of celecoxib efficacy, a multidimensional serum fractionation approach was used coupled with nanospray tandem mass spectrometry to perform label-free global proteomic profiling of serum samples from the FAP/celecoxib prevention trial. Subsequently, the application of an algorithm for large-scale biomarker discovery on comparative serum proteomic profiles of pre- and post-celecoxib treatment samples identified 83 potentially celecoxib-responsive proteins from various cellular compartments, biological processes and molecular functions. Celecoxib modulation of some of these proteins was confirmed in serum samples of FAP patients and colorectal cancer cell lines by Western blotting. Thus, using a shotgun procedure to rapidly identify important celecoxib-modulated proteins, this pilot study has uncovered novel systemic changes some of which are highly relevant for carcinogenesis and vascular biology. Validation of selected markers, especially those involved in key signaling networks and those considered molecular indicators of cardiovascular pathology, in larger celecoxib clinical trials is expected to provide insights into the molecular mechanisms of celecoxib and the efficacy/toxicity issues related to its use as a chemopreventive agent.
authors.affiliation: Molecular Oncology Program, Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi - 7520, Pakistan.
authors.forename: Naheed
authors.initials: N
authors.lastname: Fatima
authors.forename: Dirk
authors.initials: D
authors.lastname: Chelius
authors.forename: Brian T
authors.initials: BT
authors.lastname: Luke
authors.forename: Ming
authors.initials: M
authors.lastname: Yi
authors.forename: Terry
authors.initials: T
authors.lastname: Zhang
authors.forename: Stacey
authors.initials: S
authors.lastname: Stauffer
authors.forename: Robert
authors.initials: R
authors.lastname: Stephens
authors.forename: Patrick
authors.initials: P
authors.lastname: Lynch
authors.forename: Ken
authors.initials: K
authors.lastname: Miller
authors.forename: Tad
authors.initials: T
authors.lastname: Guszczynski
authors.forename: Daniel
authors.initials: D
authors.lastname: Boring
authors.forename: Peter
authors.initials: P
authors.lastname: Greenwald
authors.forename: Iqbal Unnisa
authors.initials: IU
authors.lastname: Ali
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001798:Blood Proteins / Q000378:metabolism*; D015153:Blotting, Western; D000068579:Celecoxib; D002853:Chromatography, Liquid; D019295:Computational Biology; D006801:Humans; D010446:Peptide Fragments; D040901:Proteomics; D011720:Pyrazoles / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001798:Blood Proteins; D010446:Peptide Fragments; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib