Linked Life Data

17412838

Source:http://linkedlifedata.com/resource/pubmed/id/17412838

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-5-23
pubmed:abstractText
Lung cancer cells elaborate the immunosuppressive and antiapoptotic mediator prostaglandin E(2) (PGE(2)), a product of cyclooxygenase-2 (COX-2) enzyme activity. Because peroxisome proliferator-activated receptor (PPAR)gamma ligands, such as thiazolidinediones (TZDs), inhibit lung cancer cell growth, we examined the effect of the TZDs pioglitazone and rosiglitazone on PGE(2) levels in non-small-cell lung cancer (NSCLC) A427 and A549 cells. Both TZDs inhibited PGE(2) production in NSCLC cells via a COX-2 independent pathway. To define the mechanism underlying COX-2 independent suppression of PGE(2) production, we focused on other enzymes responsible for the synthesis and degradation of PGE(2). The expression of none of the three prostaglandin synthases (microsomal PGES1, PGES2 and cystosolic PGES) was down-regulated by the TZDs. It is noteworthy that 15-hydroxyprostaglandin dehydrogenase (15-PGDH), an enzyme that produces biologically inactive 15-ketoprostaglandins from active PGE(2), was induced by TZDs. The TZD-mediated suppression of PGE(2) concentration was significantly inhibited by small interfering RNA to 15-PGDH. Studies using dominant-negative PPARgamma overexpression or 2-chloro-5-nitrobenzanilide (GW9662; a PPARgamma antagonist) revealed that the suppressive effect of the TZDs on PGE(2) is PPARgamma-independent. Together, these findings indicate that it is possible to use a clinically available pharmacological intervention to suppress tumor-derived PGE(2) by enhancing catabolism rather than blocking synthesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/15-hydroxyprostaglandin..., http://linkedlifedata.com/resource/pubmed/chemical/2,4-thiazolidinedione, http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2, http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyprostaglandin Dehydrogenases, http://linkedlifedata.com/resource/pubmed/chemical/Hypoglycemic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/PPAR gamma, http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones, http://linkedlifedata.com/resource/pubmed/chemical/pioglitazone, http://linkedlifedata.com/resource/pubmed/chemical/rosiglitazone
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1715-20
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Pioglitazone and rosiglitazone decrease prostaglandin E2 in non-small-cell lung cancer cells by up-regulating 15-hydroxyprostaglandin dehydrogenase.
pubmed:affiliation
Department of Medicine, Division of Pulmonary, Lung Cancer Research Program and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095-1690, USA. shazra@mednet.ucla.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural