15-deoxy-Delta12,14-prostaglandin J2 inhibits the expression of microsomal prostaglandin E synthase type 2 in colon cancer cells.

Abstract

Prostaglandin (PG) E(2) (PGE(2)) plays a predominant role in promoting colorectal carcinogenesis. The biosynthesis of PGE(2) is accomplished by conversion of the cyclooxygenase (COX) product PGH(2) by several terminal prostaglandin E synthases (PGES). Among the known PGES isoforms, microsomal PGES type 1 (mPGES-1) and type 2 (mPGES-2) were found to be overexpressed in colorectal cancer (CRC); however, the role and regulation of these enzymes in this malignancy are not yet fully understood. Here, we report that the cyclopentenone prostaglandins (CyPGs) 15-deoxy-Delta(12,14)-PGJ(2) and PGA(2) downregulate mPGES-2 expression in the colorectal carcinoma cell lines Caco-2 and HCT 116 without affecting the expression of any other PGES or COX. Inhibition of mPGES-2 was subsequently followed by decreased microsomal PGES activity. These effects were mediated via modulation of the cellular thiol-disulfide redox status but did not involve activation of the peroxisome proliferator-activated receptor gamma or PGD(2) receptors. CyPGs had antiproliferative properties in vitro; however, this biological activity could not be directly attributed to decreased PGES activity because it could not be reversed by adding PGE(2). Our data suggest that there is a feedback mechanism between PGE(2) and CyPGs that implicates mPGES-2 as a new potential target for pharmacological intervention in CRC.

• Authors: Oliver Schröder, Yulyana Yudina, Alan Sabirsh, Nadine Zahn, Jesper Z Haeggström, Jürgen Stein
• Journal: Journal of lipid research (J Lipid Res) Vol. 47 Issue 5 Pg. 1071-80 (May 2006) ISSN: 0022-2275 [Print] United States
• PMID: 16495511 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• 15-deoxy-delta(12,14)-prostaglandin J2
• PPAR gamma
• Prostaglandins A
• Receptors, Immunologic
• Receptors, Prostaglandin
• Intramolecular Oxidoreductases
• PTGES protein, human
• PTGES2 protein, human
• Prostaglandin-E Synthases
• prostaglandin A2
• Dinoprostone
• Prostaglandin D2
• prostaglandin D2 receptor

Topics

• Caco-2 Cells
• Colonic Neoplasms (enzymology)
• Dinoprostone (pharmacology)
• Down-Regulation
• HCT116 Cells
• Humans
• Intramolecular Oxidoreductases (antagonists & inhibitors)
• Microsomes (enzymology)
• PPAR gamma (metabolism)
• Prostaglandin D2 (analogs & derivatives, pharmacology, physiology)
• Prostaglandin-E Synthases
• Prostaglandins A (pharmacology)
• Receptors, Immunologic (metabolism)
• Receptors, Prostaglandin (metabolism)