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.