title: Impact of celecoxib on soluble intercellular adhesion molecule-1 and soluble e-cadherin concentrations in human colon cancer cell line cultures exposed to phytic acid and TNF-alpha.
abstract: Soluble adhesion molecules such as soluble intercellular adhesion molecules-1 (sICAM-1) and soluble E-cadherin (sE-cadherin) play important role in tumor invasion and the development of metastasis. It was observed that their concentrations in body fluids of patients with colon cancer were elevated. Celecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2) besides its analgesic, anti-inflammatory, and antipyretic activity is able to inhibit development of colon cancer and reduce risk of metastasis. The additional factors, e.g., dietary components in colon cancer, may influence therapeutic effect of drugs, such as cytokines. TNF-alpha (tumor necrosis factor - alpha) is a cytokine, which concentration significantly increases in serum of patients with inflammatory and cancer diseases. The latest studies demonstrate, that phytic acid (IP6), a myo-inositol derivative, abundantly present in high-fiber diets could substantially reduce colon cancer incidence. The aim of the present study was to evaluate the influence of celecoxib on sICAM-1 and sE-cadherin concentrations in transformed epithelial colon cell cultures simultaneously exposed to IP6 and TNF-alpha. Additionally, the adhesion of the exposed cells to collagen I was assessed. HT-29 and Caco-2 cells were cultured in the presence of 50 ng/mL celecoxib, 1.0 mM IP6, and 100 ng/mL TNF-alpha, and their combination: TNF-alpha plus IP6, TNF-alpha plus celecoxib, IP6 plus celecoxib, and TNF-alpha with celecoxib plus IP6, for 96 h. Nonexposed cell line cultures served as controls. Concentrations of sICAM-1 and sE-cadherin were measured in the culture medium by enzyme-linked immunosorbent assay (ELISA) using Quantikine - Human sICAM-1/CD54 Immunoassay and Quantikine-Human sE-Cadherin Immunoassay. All the results obtained were expressed as ng per mL. In the adhesion assay, the cells were incubated with IP6 (0.5, 1.0 and 2.0 mM), TNF-alpha (100 ng/mL), celecoxib (50 ng/mL) and their combination for 90 min. Fluorescence values 480 nm/530 nm reflected concentrations of DNA in cells attached to collagen I. The obtained results indicate that celecoxib (50 ng/mL), the selective COX-2 inhibitor, reduces significantly sICAM-1 and sE-cadherin concentrations in HT-29 and Caco-2 transformed human epithelial colorectal cell line cultures co-treated with IP6 (1.0 mM) and TNF-alpha (100 ng/mL). A decrease of cells adhesion property to collagen I was observed under the influence of 50 ng/mL celecoxib on cell cultures exposed to 1.0 or 2.0 mM IP6 and 1.0 or 2.0 mM IP6 plus 100 ng/mL TNF-alpha.
authors.affiliation: Department of Biochemistry, School of Pharmacy, Medical University of Silesia, Sosnowiec, Poland. bparfiniewicz@sum.edu.pl
authors.forename: Beata
authors.initials: B
authors.lastname: Parfiniewicz
authors.forename: Joanna
authors.initials: J
authors.lastname: Pendzich
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Gruchlik
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hollek
authors.forename: Ludmiła
authors.initials: L
authors.lastname: Weglarz
mesh_terms: D018938:Caco-2 Cells; D015820:Cadherins / Q000032:analysis*; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis*; D010833:Phytic Acid / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D015820:Cadherins; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D010833:Phytic Acid; D000068579:Celecoxib