Published online Nov 7, 2015. doi: 10.3748/wjg.v21.i41.11748
Peer-review started: May 6, 2015
First decision: June 2, 2015
Revised: June 25, 2015
Accepted: August 31, 2015
Article in press: August 31, 2015
Published online: November 7, 2015
Enzymatic metabolism of the 20C polyunsaturated fatty acid (PUFA) arachidonic acid (AA) occurs via the cyclooxygenase (COX) and lipoxygenase (LOX) pathways, and leads to the production of various bioactive lipids termed eicosanoids. These eicosanoids have a variety of functions, including stimulation of homeostatic responses in the cardiovascular system, induction and resolution of inflammation, and modulation of immune responses against diseases associated with chronic inflammation, such as cancer. Because chronic inflammation is essential for the development of colorectal cancer (CRC), it is not surprising that many eicosanoids are implicated in CRC. Oftentimes, these autacoids work in an antagonistic and highly temporal manner in inflammation; therefore, inhibition of the pro-inflammatory COX-2 or 5-LOX enzymes may subsequently inhibit the formation of their essential products, or shunt substrates from one pathway to another, leading to undesirable side-effects. A better understanding of these different enzymes and their products is essential not only for understanding the importance of eicosanoids, but also for designing more effective drugs that solely target the inflammatory molecules found in both chronic inflammation and cancer. In this review, we have evaluated the cancer promoting and anti-cancer roles of different eicosanoids in CRC, and highlighted the most recent literature which describes how those molecules affect not only tumor tissue, but also the tumor microenvironment. Additionally, we have attempted to delineate the roles that eicosanoids with opposing functions play in neoplastic transformation in CRC through their effects on proliferation, apoptosis, motility, metastasis, and angiogenesis.
Core tip: Eicosanoids are bioactive lipids generated from polyunsaturated fatty acids (usually arachidonic acid) through highly regulated enzymatic pathways in many different cell types. These molecules are effective in small amounts, and may act in an autocrine or paracrine manner to regulate some of the most important steps in the development of acute inflammation and its resolution. Aberrant expression of the enzymes that help synthesize these bioactive lipids is frequently seen in diseases associated with chronic inflammation, including cancer.