Eicosanoid pathway in colorectal cancer: Recent updates

Figure 1 Enzymatic metabolism of polyunsaturated fatty acid can generate bioactive lipids that induce inflammation, tumorigenesis, and thrombosis, while also generating mediators with anti-tumorigenic, pro-resolution properties. In the pro-tumorigenic arm, arachidonic acid (AA) is metabolized via the cyclooxygenase (COX) pathway to generate prostaglandins (PGE₂, PGI₂) and thromboxanes (TxA₂). Lipoxygenase (LOX) enzymes convert AA to hydroxyeicosatetraenoic acids (HETEs), which are active on their own, or can be further converted to leukotrienes (LTs). In the anti-tumorigenic, pro-resolution arm, metabolism of AA through 15-LOX1/2 or acetyl salicylic acid (ASA) acetylated COX-2 generates intermediates that can be converted to lipoxins (Lxs) through the transcellular activity of other LOXs (5- or 12-LOX). Conversion of linoleic acid (LA) to 13(S)-HODE may produce anti-inflammatory effects mediated through activation of PPARγ. The fish oils eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be converted by acetylated COX-2 to pro-resolution mediators E- and D- series resolvins (Rvs), respectively. PUFA: Polyunsaturated fatty acid.