Role of microsomal prostaglandin E synthase-1 (mPGES-1)-derived prostaglandin E2 in colon carcinogenesis

• mPGES-1 is highly expressed in human colorectal cancer tissues.
• Genetic deletion of mPGES-1 suppressed colon carcinogenesis in mouse models.
• PGE2 receptors (EPs) are involved in colon carcinogenesis.
• 15-PGDH functions as a suppressor of colon carcinogenesis.
• mPGES-1, EPs and 15-PGDH are attractive as novel drug targets for colorectal cancer.

Nonsteroidal anti-inflammatory drugs, especially selective cyclooxygenase-2 (COX-2) inhibitors, are among the most promising chemopreventive agents for colorectal cancer. However, recent clinical trials have indicated that these inhibitors pose a significantly increased cardiovascular risk. Microsomal prostaglandin E (PGE) synthase-1 (mPGES-1) and mPGES-1-derived PGE2 have gained attention recently as alternative targets to COX-2 for colorectal cancer chemoprevention and chemotherapy. In this review, we summarize the current understanding of the roles of mPGES-1, a PGE2-inactivating enzyme (15-hydroxyprostagladin dehydrogenase), and PGE2 specific receptors (EPs) in colon carcinogenesis.