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.