TY - JOUR
T1 - MPGES-1 as a target for cancer suppression. A comprehensive invited review "Phospholipase A2 and lipid mediators"
AU - Nakanishi, Masako
AU - Gokhale, Vijay
AU - Meuillet, Emmanuelle J.
AU - Rosenberg, Daniel W.
PY - 2010/6
Y1 - 2010/6
N2 - Prostaglandin E2 (PGE2) is a bioactive lipid that can elicit a wide range of biological effects associated with inflammation and cancer. The physiological roles of PGE2 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 PGE2 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.
AB - Prostaglandin E2 (PGE2) is a bioactive lipid that can elicit a wide range of biological effects associated with inflammation and cancer. The physiological roles of PGE2 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 PGE2 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.
KW - Cancer
KW - Inflammation
KW - MPGES-1
KW - MPGES-1 inhibitor
KW - PGE
UR - http://www.scopus.com/inward/record.url?scp=77953290938&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953290938&partnerID=8YFLogxK
U2 - 10.1016/j.biochi.2010.02.006
DO - 10.1016/j.biochi.2010.02.006
M3 - Short survey
C2 - 20159031
AN - SCOPUS:77953290938
SN - 0300-9084
VL - 92
SP - 660
EP - 664
JO - Biochimie
JF - Biochimie
IS - 6
ER -