INFLUENCE OF INOSITOL HEXAPHOSPHATE ON THE EXPRESSION OF SELECTED PROLIFERATION MARKERS IN IL-1β-STIMULATED INTESTINAL EPITHELIAL CELLS

The aim of the present study was to examine the influence of IP6, a naturally occurring phytochemical, on the expression of genes coding for proliferation markers, i.e., cyclin D1 (CCND1) and histone H3 in IL-1 beta-stimulated intestinal cancer cell line Caco-2. Quantification of genes expression was carried out using real time RT-QPCR technique in Caco-2 cells after treatment with IL-1 beta, 1 and 2.5 mM of IP6 for 3, 6 and 12 h. In separate cultures, cells were incubated with IL-1 beta for the indicated times. The untreated Caco-2 cells were used as the control. In a time course experiment, stimulation of cells with IL-1 beta only resulted in an overex- pression of both CCND1 and histone H3 mRNAs as compared with control. IP6 had no influence on IL-1 beta-stimulated CCND1 expression for 3 and 6 h. After 12 h, statistically significant decrease in CCND1 mRNA was observed in cells exposed to IL-1 beta and IP6 (1 and 2.5 mM) in relation to cells treated with IL-1 beta only. The levels of H3 mRNA in IL-1 beta-stimulated cells and cells treated with IL-1 beta and IP6 revealed no statistically significant differences after 3 h. IP6 at 1 and 2.5 mM enhanced IL-1 beta-stimulated transcription of H3 gene after 6 h. Subsequently (12 h), the combination of IP6 and IL-1 beta decreased H3 mRNA level compared to IL1 beta-treated cells. In conclusion, pro-inflammatory cytokine IL-1 beta up-regulates CCND1 and histone H3 mRNAs expression in Caco-2 cells. These results suggest that the ability of IP6 to inhibit colon cancer cells proliferation may be mediated through downregulation of genes encoding cyclin D1 and histone H3 at the mRNA level.