Figure 1.

Schematic view of fatty acid pathways relevant to formation of eicosanoids in normal and tumor tissues. Fatty acids from endogenous synthesis and diet contribute to the fatty acid composition of cellular lipids stores in membranes and lipid droplets and modulate the relative proportion of arachidonic acid (ω-6) that is available to cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 enzymes for production of oxygenated metabolites. Lipoxygenases selectively produce S-isomeric eicosanoids while lipid peroxidation produces R and S isomers in equal quantities. All of these enzymes use arachidonic acid as a substrate except that 13-HODE is produced from linoleic acid. Prostaglandin E₂ is produced from arachidonic acid by both COX-1 and COX-2, and prostaglandin E₃ is produced from eicosapentaenoic acid (ω-3) by COX-2, although eicosapentaenoic acid competes poorly with arachidonic acid as a substrate for COX-2. As discussed in the text, products that have been associated with beneficial effects in the colon include prostaglandin E₃, 13-S-HODE and 15-S-HETE while the other eicosanoids shown generally have pro-tumorigenic effects. Prostaglandin E₂ in particular is known to be promote colon tumorigenesis.