TY  - JOUR
A1  - Schröder, Oliver
A1  - Yudina, Yulyana
A1  - Sabirsh, Alan
A1  - Zahn, Nadine
A1  - Haeggström, Jesper Z.
A1  - Stein, Jürgen
T1  - 15-deoxy-Δ12,14-prostaglandin J2 inhibits the expression of microsomal prostaglandin E synthase type 2 in colon cancer cells
T2  - Journal of lipid research
N2  - Prostaglandin (PG) E2 (PGE2) plays a predominant role in promoting colorectal carcinogenesis. The biosynthesis of PGE2 is accomplished by conversion of the cyclooxygenase (COX) product PGH2 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-Δ12,14-PGJ2 and PGA2 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 γ or PGD2 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 PGE2. Our data suggest that there is a feedback mechanism between PGE2 and CyPGs that implicates mPGES-2 as a new potential target for pharmacological intervention in CRC.
KW  - colorectal cancer
KW  - cyclopentenone prostaglandins
KW  - feedback control
KW  - proliferation
KW  - prostaglandin E
KW  - redox status
Y1  - 2006
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/75536
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-755368
SN  - 0022-2275
VL  - 47
IS  - 5
SP  - 1071
EP  - 1080
PB  - Elsevier
CY  - Amsterdam
ER  -