Korean J Gastroenterol.  2008 May;51(5):274-279.

Role of Prostaglandins in Colon Cancer

• Myung SJ
• Kim IH

Abstract

Colon cancer is one of the major leading causes of cancer-related deaths in the Western countries. In Korea, the incidence of colon cancer is increasing due to changes in environment and lifestyle such as diet. Chemoprevention strategy using non-steroidal anti-inflammatory drugs (NSAIDs) has been under intensive clinical and epidemiological research as these drugs suppress colorectal cancer. The best known targets of NSAIDs are cyclooxygenase (COX) enzymes, which convert arachidonic acid to prostaglandins (PGs) and thromboxane. Among these PGs, prostaglandin E2 (PGE2) can promote tumor growth by binding its receptors and activating signal pathways which control cell proliferation, migration, apoptosis, and angiogenesis. Therefore, COX inhibition is promising approach for chemoprevention of colorectal cancer. However, the prolonged use of COX-2 inhibitors is associated with unacceptable cardiovascular side effects. Thus, new targets involved in PGs metabolism are under investigation. 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a key metabolic enzyme of PGE2, was up-regulated in normal colonic epithelium, but decreased in colon cancer. Recent findings suggest that 15-PGDH is involved in the neoplastic progression of initiated colonic epithelial cells. Also, new players related with PGs metabolism including prostaglandin transporter (PGT) and microsomal prostaglandin E synthase (mPGES) were reported to play a role in colorectal cancer development. This review presents current knowledge about the role of prostaglandins and associated proteins in colorectal cancer development and progression.

Keyword

Prostaglandin; Colon cancer; 15-hydroxyprostaglandin dehydrogenase; Carcinogenesis

MeSH Terms

Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
Colonic Neoplasms/drug therapy/*etiology/prevention & control
Cyclooxygenase 2/metabolism
Cyclooxygenase Inhibitors/pharmacology/therapeutic use
Humans
Hydroxyprostaglandin Dehydrogenases/antagonists & inhibitors/metabolism
Prostaglandins/metabolism/*physiology