Original Research ArticleModulating effect of inositol hexaphosphate on arachidonic acid-dependent pathways in colon cancer cells

- The Caco-2 cells constitutively express genes encoding COX-1 and COX-2 and LOX isoforms (5-LOX, 12-LOX, 15-LOX).
- Our data provide new knowledge of the effects of IP6 on the expression of COX and LOX genes in colon cancer cells.
- Pro-inflammatory factors modulate mRNA expression of genes encoding COX and LOX isoforms in time-dependent manner.
- IP6 inhibits the expression of mRNA and protein of COX-2 and subsequently synthesis of PGE2.
- COX inhibition by IP6 leads to an increased availability of arachidonic acid for lipoxygenase pathway.

Cyclooxygenase (COX) and lipoxygenase (LOX) are key enzymes of arachidonic acid metabolism. Their products, prostaglandins and leukotrienes, are involved in the pathogenesis of inflammatory bowel diseases and colorectal cancer. The aim of the study was to examine the influence of inositol hexaphosphate (IP6), a naturally occurring phytochemical, on the expression of genes encoding COX and LOX isoforms and synthesis of their products (PGE2 and LTB4) in colon cancer cell line Caco-2 stimulated with pro-inflammatory agents (IL-1β/TNFα). Real-time RT-qPCR was used to validate mRNAs level of examined genes. The concentrations of COX-2 and 5-LOX proteins as well as PGE2 and LTB4 were determined by the ELISA method. Based on these studies it may be concluded that IP6 may limit inflammatory events in the colonic epithelium and prevent colon carcinomas by modulating the expression of genes encoding COX and LOX isoforms at both mRNA and protein levels as well as by affecting the synthesis and secretion of prostaglandins and leukotrienes.