The inhibitory effect of celecoxib on mouse hepatoma H22 cell line on the arachidonic acid metabolic pathway

Citation metadata

Date: Aug. 2010
From: Biochemistry and Cell Biology(Vol. 88, Issue 4)
Publisher: NRC Research Press
Document Type: Report
Length: 4,621 words
Lexile Measure: 1350L

Document controls

Main content

Abstract :

Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2). It may reduce the risk of cancer formation by affecting the metabolism of arachidonic acid (AA), which has been implicated in the development of cancer. Accordingly, this study was designed to determine the effects of celecoxib on the AA pathway in mouse hepatoma H22 cells. Celecoxib was found to inhibit the proliferation of H22 cells in a dose- and time-dependent manner. Low doses (50 and 100 [micro]mol x [L.sup.-1]) of celecoxib caused an increase in the expression of cytosolic phospholipase [A.sub.2] ([cPLA.sub.2]), but did not affect the expression of COX-2 in terms of the mRNA and protein levels. Surprisingly, the amount of AA was elevated and the level of prostaglandin [E.sub.2] ([PGE.sub.2]) was unaltered in the culture supernatant. At higher celecoxib doses (200 and 400 [micro]mol x [L.sup.-1]), the mRNA and protein of both COX-2 and [cPLA.sub.2] were inhibited. The concentration of AA was increased, and [PGE.sub.2] level was depressed in H22 cells. The ratio of AA to [PGE.sub.2] was increased in a dose-dependent manner. Our findings suggest that the imbalance between AA and [PGE.sub.2], characterized by increased AA at a low dosage and decreased [PGE.sub.2] at a high dosage of celecoxib, was an important indicator of cytotoxicity of celecoxib on H22 cells. Key words: celecoxib, cyclooxygenase-2, cytosolic phospholipase A2, arachidonic acid, prostaglandin [E.sub.2]. Le celecoxib est un inhibiteur selectif de la cyclooxygenase-2 (COX-2). Il peut reduire le risque de formation de cancer en modifiant le metabolisme de l'acide arachidonique (AA) implique dans le developpement du cancer. Consequemment, cette etude a ete concjue pour determiner les effets du celecoxib sur la voie de l'AA dans les cellules d'hepatome de souris H22. Dans cette etude, le celecoxib a inhibe la proliferation des cellules H22 de facon dependante de la concentration et du temps. De faibles doses (50 [micro]mol x [L.sup.-1] et 100 [micro]mol x [L.sup.-1])de celecoxib ont cause une augmentation de l'expression de la phospholipase A2 cytosolique ([cPLA.sub.2]), mais n'ont pas affecte l'expression de l'ARNm et de la proteine COX-2. De facon surprenante, la quantite d'AA etait elevee et le niveau de prostaglandine [E.sub.2] ([PGE.sub.2]) du milieu de culture n'etait pas modifie. A plus fortes doses de celecoxib (200 [micro]mol x [L.sup.-1] et 400 [micro]mol x [L.sup.-1]), l'expression des proteinesCOX-2 et [cPLA.sub.2] et de leur ARNm etait inhibee. La concentration d'AA etait augmentee et le niveau de [PGE.sub.2] des cellules H22 etait diminue. Le ratio AA/[PGE.sub.2] etait augmented de facon dependante de la concentration. Nos resultats suggerent qu'un desequilibre entre les quantites d'AA et de [PGE.sub.2] caracterise par une augmentation d'AA a faible dose et une diminution de [PGE.sub.2] a forte dose de celecoxib, constituait un indicateur important de la cytotoxicite du celecoxib sur les cellules H22. Mots-cles: celecoxib, cyclooxygenase-2, phospholipase [A.sub.2], acide arachidonique, prostaglandine [E.sub.2]. [Traduit par la Redaction]

Source Citation

Source Citation   

Gale Document Number: GALE|A243798993