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Impact of celecoxib on soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-cadherin (sE-cadherin) concentrations in human colon cancer cell line cultures exposed to phytic acid (IP6) and TNF-α (tumor necrosis factor-alpha)

Beata Parfiniewicz 1Joanna Pendzich 2Arkadiusz R. Gruchlik 3Andrzej Hollek 1Ludmiła Węglarz 1

1. Departament of Biochemistry, Medical University of Silesia, Narcyzow 1, Sosnowiec 41-200, Poland
2. The Third Uniwersity Hospital, Koziolka 1, Zabrze 41-800, Poland
3. Department of Biopharmacy, Medical University of Silesia, Narcyzów 1, Sosnowiec 41-200, Poland


 Information about discovery of antineoplastic activity of non-oncological drugs spreads very quickly. One of them seems to be a class of non-steroidal anti-inflammatory drugs (NSAIDs), coxibs. Celecoxib, a NSAIDs representant selectively inhibit cyclooxygenase-2 (COX-2), an enzyme that activate synthesis of prostaglandines, pro-inflammatory molecules, that promote inflammation. Analysis of COX-2 gene expression in colonic epithelium showed that it’s level was significantly elevated in colon cancer and familial adenomatous polyposis. There are scientific reports that celecoxib, besides it’s  analgesic, anti-inflammatory, and antipyretic activity is able to inhibit development of colon cancer and  reduce risk of liver colon cancer metastasis. It is well known that these molecules play a key role in carcinogenesis. The measurement of their concentrations in serum and in other patient’s body fluids may be helpful for diagnostics, advancement evaluation, and therapy response monitoring in patients with different types of cancer. The additional factors, e.g. dietary components in colon cancer, may influence therapeutic effect of drugs, such as cytokines. TNF-α (tumor necrosis factor - alpha) is a cytokine, which concentration significantly increases in serum of patients with inflammatory and cancer diseases. Last studies demonstrate, that phytic acid (IP6), a phosphorylated carbohydrate, abundantly present in high-fiber diets could substantially reduce colon cancer incidence.

The aim of the present study was to estimate the influence of celecoxib on sICAM-1 and sE-cadherin concentrations in transformed epithelial colon cell cultures simultaneously exposed to IP6 and TNF- α. Human intestinal HT-29 and Caco-2 cell lines derived from colon adenocarcinoma were used in our studies.  The cells were cultured in the presence of 50 ng/ml celecoxib (f.c.) 1.0 mM IP6, and 100 ng/ml TNF-α and their combination: TNF-α plus IP6, TNF-α plus celecoxib, IP6 plus celecoxib, and TNF-α with celecoxib plus IP6, for 96 hours. 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 (R&D Systems) and Quantikine–Human sE-Cadherin Immunoassay (R&D Systems). All the results obtained were expressed as ng per ml. The statistical analysis was performed with the use of Statistica 10.0 Software. 

The results of this studies showed that mean sICAM-1 concentration in HT-29 cell line control culture was 2.26 ng/ml (+/- 0.13), while in the control Caco-2 cell line culture amounted 5.56 ng/ml (+/-0.58). Celecoxib (50 ng/ml) alone as well as in the presence of 1 mM IP6 or TNF-α did not cause a significant change in this adhesion molecule concentrations in Caco-2 and HT-29 cell lines either. In both cell line types exposed to a combination of celecoxib, IP6 and TNF-α a statistically significant decrease in sICAM-1 level was observed compared with the cell cultures exposed to a combination of IP6 plus TNF-α. In HT-29 cell line culture sICAM-1 concentration was statistically significantly higher, than in the control culture because of high concentration of the molecule deriving from TNF-α exposed cells, but the effect was not observed in Caco-2 cell line cultures. Mean sE-cadherin concentrations in HT-29 and Caco-2 cell line cultures were 17.34 ng/ml (+/- 1.2) and 16.23 ng/ml (+/-0.78), respectively. There was no significant difference in sE-cadherin concentration in HT-29 cell line culture exposed to celecoxib compared with the control one, but in Caco-2 cell line culture  it was significantly lower. The addition of celecoxib to the HT-29 cell line culture containing TNF-α did not cause changes in sE-cadherin concentration compared with cell culture containing the cytokine exclusively, while in Caco-2 cell line culture it was significantly lower  than in culture containing only  the cytokine. In both, HT-29 and Caco-2 cell lines, low sE-cadherin concentrations were observed in the presence of celecoxib introduced along with 1 mM IP6. Co-treatment with celecoxid, IP6 and TNF-α caused a significant decrease in sE-cadherin concentrations in culture medium deriving from HT-29 and Caco-2 cell lines down to 0.5 ng/ml (+/-0.4) and  2.1 ng/ml (+/-1.1), respectively. 


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Presentation: Poster at VIII Multidyscyplinarna Konferencja Nauki o Leku, by Beata Parfiniewicz
See On-line Journal of VIII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2012-03-15 12:03
Revised:   2012-03-15 12:03