15-deoxy-Δ12,14-prostaglandin J2 inhibits the expression of microsomal prostaglandin E synthase type 2 in colon cancer cells
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 (m...
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doaj-015c964e76ae4eafb6fb2b28edb6f94c2021-04-27T04:44:41ZengElsevierJournal of Lipid Research0022-22752006-05-014751071108015-deoxy-Δ12,14-prostaglandin J2 inhibits the expression of microsomal prostaglandin E synthase type 2 in colon cancer cellsOliver Schroäder0Yulyana Yudina1Alan Sabirsh2Nadine Zahn3Jesper Z. Haeggstroäm4Juärgen Stein5First Department of Medicine, Division of Gastroenterology, Center for Drug Research, Development and Saftey (ZAFES), Johann Wolfgang Goethe University, 60590 Frankfurt/Main, GermanyFirst Department of Medicine, Division of Gastroenterology, Center for Drug Research, Development and Saftey (ZAFES), Johann Wolfgang Goethe University, 60590 Frankfurt/Main, GermanyDepartment of Medical Biochemistry and Biophysics, Division of Chemistry II, Karolinska Institutet, 17177 Stockholm, SwedenFirst Department of Medicine, Division of Gastroenterology, Center for Drug Research, Development and Saftey (ZAFES), Johann Wolfgang Goethe University, 60590 Frankfurt/Main, GermanyDepartment of Medical Biochemistry and Biophysics, Division of Chemistry II, Karolinska Institutet, 17177 Stockholm, SwedenFirst Department of Medicine, Division of Gastroenterology, Center for Drug Research, Development and Saftey (ZAFES), Johann Wolfgang Goethe University, 60590 Frankfurt/Main, GermanyProstaglandin (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.http://www.sciencedirect.com/science/article/pii/S0022227520332569colorectal cancercyclopentenone prostaglandinsfeedback controlproliferationprostaglandin E2redox status |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Oliver Schroäder Yulyana Yudina Alan Sabirsh Nadine Zahn Jesper Z. Haeggstroäm Juärgen Stein |
spellingShingle |
Oliver Schroäder Yulyana Yudina Alan Sabirsh Nadine Zahn Jesper Z. Haeggstroäm Juärgen Stein 15-deoxy-Δ12,14-prostaglandin J2 inhibits the expression of microsomal prostaglandin E synthase type 2 in colon cancer cells Journal of Lipid Research colorectal cancer cyclopentenone prostaglandins feedback control proliferation prostaglandin E2 redox status |
author_facet |
Oliver Schroäder Yulyana Yudina Alan Sabirsh Nadine Zahn Jesper Z. Haeggstroäm Juärgen Stein |
author_sort |
Oliver Schroäder |
title |
15-deoxy-Δ12,14-prostaglandin J2 inhibits the expression of microsomal prostaglandin E synthase type 2 in colon cancer cells |
title_short |
15-deoxy-Δ12,14-prostaglandin J2 inhibits the expression of microsomal prostaglandin E synthase type 2 in colon cancer cells |
title_full |
15-deoxy-Δ12,14-prostaglandin J2 inhibits the expression of microsomal prostaglandin E synthase type 2 in colon cancer cells |
title_fullStr |
15-deoxy-Δ12,14-prostaglandin J2 inhibits the expression of microsomal prostaglandin E synthase type 2 in colon cancer cells |
title_full_unstemmed |
15-deoxy-Δ12,14-prostaglandin J2 inhibits the expression of microsomal prostaglandin E synthase type 2 in colon cancer cells |
title_sort |
15-deoxy-δ12,14-prostaglandin j2 inhibits the expression of microsomal prostaglandin e synthase type 2 in colon cancer cells |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2006-05-01 |
description |
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. |
topic |
colorectal cancer cyclopentenone prostaglandins feedback control proliferation prostaglandin E2 redox status |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520332569 |
work_keys_str_mv |
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