Title: Proapoptotic and antiproliferative potential of selective cyclooxygenase-2 inhibitors in human liver tumor cells
Abstract: HepatologyVolume 36, Issue 4 p. 885-894 Original ArticlesFree Access Proapoptotic and antiproliferative potential of selective cyclooxygenase-2 inhibitors in human liver tumor cells Michael André Kern, Michael André Kern From the Institute of Pathology, University of Cologne, Cologne, GermanySearch for more papers by this authorDominic Schubert, Dominic Schubert From the Institute of Pathology, University of Cologne, Cologne, GermanySearch for more papers by this authorDina Sahi, Dina Sahi From the Institute of Pathology, University of Cologne, Cologne, GermanySearch for more papers by this authorMirja Mareike Schöneweiß, Mirja Mareike Schöneweiß From the Institute of Pathology, University of Cologne, Cologne, GermanySearch for more papers by this authorIlona Moll, Ilona Moll From the Institute of Pathology, University of Cologne, Cologne, GermanySearch for more papers by this authorAnke Maria Haugg, Anke Maria Haugg From the Institute of Pathology, University of Cologne, Cologne, GermanySearch for more papers by this authorHans Peter Dienes, Hans Peter Dienes From the Institute of Pathology, University of Cologne, Cologne, GermanySearch for more papers by this authorKai Breuhahn, Kai Breuhahn From the Institute of Pathology, University of Cologne, Cologne, GermanySearch for more papers by this authorPeter Schirmacher, Corresponding Author Peter Schirmacher [email protected] From the Institute of Pathology, University of Cologne, Cologne, GermanyInstitute of Pathology, University of Cologne, Joseph-Stelzmann-Str. 9, D-50931 Cologne, Germany. fax: (49) 221-478-6360.===Search for more papers by this author Michael André Kern, Michael André Kern From the Institute of Pathology, University of Cologne, Cologne, GermanySearch for more papers by this authorDominic Schubert, Dominic Schubert From the Institute of Pathology, University of Cologne, Cologne, GermanySearch for more papers by this authorDina Sahi, Dina Sahi From the Institute of Pathology, University of Cologne, Cologne, GermanySearch for more papers by this authorMirja Mareike Schöneweiß, Mirja Mareike Schöneweiß From the Institute of Pathology, University of Cologne, Cologne, GermanySearch for more papers by this authorIlona Moll, Ilona Moll From the Institute of Pathology, University of Cologne, Cologne, GermanySearch for more papers by this authorAnke Maria Haugg, Anke Maria Haugg From the Institute of Pathology, University of Cologne, Cologne, GermanySearch for more papers by this authorHans Peter Dienes, Hans Peter Dienes From the Institute of Pathology, University of Cologne, Cologne, GermanySearch for more papers by this authorKai Breuhahn, Kai Breuhahn From the Institute of Pathology, University of Cologne, Cologne, GermanySearch for more papers by this authorPeter Schirmacher, Corresponding Author Peter Schirmacher [email protected] From the Institute of Pathology, University of Cologne, Cologne, GermanyInstitute of Pathology, University of Cologne, Joseph-Stelzmann-Str. 9, D-50931 Cologne, Germany. fax: (49) 221-478-6360.===Search for more papers by this author First published: 30 December 2003 https://doi.org/10.1053/jhep.2002.36125Citations: 120AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Recent studies have shown increased levels of cyclooxygenase-2 (COX-2) in a variety of human malignancies, including hepatocellular carcinoma (HCC), but so far it is unknown whether COX-2 contributes to the malignant growth and whether inhibition of COX-2 function modifies the malignant potential of liver tumors. COX-1 and COX-2 expression was determined in 4 liver tumor cell lines (Hep 3B, HuH-7, Hep G2, Sk-hep1) by Northern hybridization and Western immunoblot. The functional effects of the nonselective inhibitor sulindac sulfide and the COX-2 selective inhibitors SC-58635 and meloxicam were examined by 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide (MTT)-assays and BrdU uptake, morphology, and TUNEL analysis of apoptosis. Apoptosis regulating proteins were analyzed by Western immunoblot. COX-1 and COX-2 expression was demonstrable in all tested liver tumor cell lines. Sulindac sulfide (50 to 400 μmol/L), SC-58635 (6,25 to 400 μmol/L), and meloxicam (6.25 to 400 μmol/L) led to a significant time- and dose-dependent reduction of cell numbers of up to 80% (P < .05). At equimolar concentrations the effect was more pronounced when COX-2 was selectively blocked. COX-2 inhibition induced apoptosis and reduced tumor cell proliferation. Apoptosis after COX-2 inhibition with SC-58635 (50 μmol/L) was independent of BCL-2, BAX, and the phosphorylation status of AKT/PKB and BAD, but correlated with activation of caspase-9, caspase-3, and caspase-6. In conclusion, selective inhibition of COX-2 leads to a marked growth inhibition of human liver tumor cells, based on the induction of apoptosis and inhibition of proliferation and, thus, may offer therapeutic and preventive potential in human hepatocarcinogenesis. Citing Literature Volume36, Issue4October 2002Pages 885-894 ReferencesRelatedInformation