NS398, A SELECTIVE CYCLOOXYGENASE-2 INHIBITOR, INDUCES APOPTOSIS AND DOWN-REGULATES BCL-2 EXPRESSION IN LNCAP CELLS

Cyclooxygenase (COX)-2, an inducible enzyme that catalyzes the formati on of prostaglandins and other eicosanoids from arachidonic acid, is c onstitutively expressed in LNCaP human prostate cancer cell line. To e valuate the potential role of COX-2 in prostate cancer, LNCaP cells we re treated with NS398, a selective COX-2 inhibitor, and the effects on cell viability and apoptosis were determined. NS398 treatment induced apoptosis in LNCaP cells in a time- and dose-dependent fashion. Treat ment with 100 mu M NS398 caused a down-regulation in bcl-2 protein exp ression, followed by chromatin condensation, chromosomal DNA fragmenta tion, and changes in nuclear morphology detected by 4,6-diamidino-2-ph enylindole staining, DNA fragmentation assay, and terminal deoxynucleo tidyl transferase-mediated UTP-biotin nick end-labeling assay. In cont rast, NS398 treatment had no effect on either cell viability or nuclea r function and morphology in human fetal prostate fibroblasts, These r esults demonstrate that NS398 induces apoptosis in LNCaP cells but not in human fetal prostate fibroblasts, and that this induction is assoc iated with a decreased level of bcl-2 protein.