15-deoxy-Delta12,14-prostaglandin J2 inhibits the expression of microsomal prostaglandin E synthase type 2 in colon cancer cells
(2006) In Journal of Lipid Research 47(5). p.1071-1071- 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.... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1136952
- author
- Schroder, Oliver ; Yudina, Yulyana LU ; Sabirsh, Alan ; Zahn, Nadine ; Haeggstrom, Jesper Z and Stein, Jurgen
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- 15d-PGJ2, colorectal cancer, cyclopentenone prostaglandins, feedback control, mPGES-2, proliferation, PGE2, redox status
- in
- Journal of Lipid Research
- volume
- 47
- issue
- 5
- pages
- 1071 - 1071
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- pmid:16495511
- scopus:33646814714
- pmid:16495511
- ISSN
- 1539-7262
- DOI
- 10.1194/jlr.M600008-JLR200
- language
- English
- LU publication?
- yes
- id
- 47567b5f-e6ce-4c58-aec5-6234afc4f686 (old id 1136952)
- date added to LUP
- 2016-04-01 11:43:16
- date last changed
- 2022-01-26 17:12:10
@article{47567b5f-e6ce-4c58-aec5-6234afc4f686,
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.}},
author = {{Schroder, Oliver and Yudina, Yulyana and Sabirsh, Alan and Zahn, Nadine and Haeggstrom, Jesper Z and Stein, Jurgen}},
issn = {{1539-7262}},
keywords = {{15d-PGJ2; colorectal cancer; cyclopentenone prostaglandins; feedback control; mPGES-2; proliferation; PGE2; redox status}},
language = {{eng}},
number = {{5}},
pages = {{1071--1071}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Lipid Research}},
title = {{15-deoxy-Delta12,14-prostaglandin J2 inhibits the expression of microsomal prostaglandin E synthase type 2 in colon cancer cells}},
url = {{http://dx.doi.org/10.1194/jlr.M600008-JLR200}},
doi = {{10.1194/jlr.M600008-JLR200}},
volume = {{47}},
year = {{2006}},
}