mPGES-1 as a target for cancer suppression: A comprehensive invited review "Phospholipase A2 and lipid mediators".
Prostaglandin E(2) (PGE(2)) is a bioactive lipid that can elicit a wide range of biological effects associated with inflammation and cancer. The physiological roles of PGE(2) are diverse, mediated in part through activation of key downstream signaling cascades via transmembrane EP receptors located on the cell surface. Elevated levels of COX-2 and concomitant overproduction of PGE(2) are often found in human cancers. These observations have led to the use of non-steroidal anti-inflammatory drugs (NSAIDs) as chemopreventive agents, particularly for colorectal cancer (CRC). Their long-term use, however, may be associated with gastrointestinal toxicity and increased risk of adverse cardiovascular events, prompting the development of other enzymatic targets in this pathway. This review will focus on recent efforts to target the terminal synthase, mPGES-1, for cancer chemoprevention. The role of mPGES-1 in the pathogenesis of various cancers is discussed. In addition, an overview of recent efforts to develop small molecule inhibitors that target the protein with high selectivity is also be reviewed.
Center for Molecular Medicine, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030-3101, USA.
Masako
M
Nakanishi
Vijay
V
Gokhale
Emmanuelle J
EJ
Meuillet
Daniel W
DW
Rosenberg
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000502:physiology*; D009369:Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000517:prevention & control*; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism; D000071876:Prostaglandin-E Synthases
D000894:Anti-Inflammatory Agents, Non-Steroidal; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases