Cyclooxygenase (COX)-2, an inducible enzyme that catalyzes the formation of prostaglandins and other eicosanoids from arachidonic acid, is constitutively expressed in LNCaP human prostate cancer cell line. To evaluate the potential role of COX-2 in prostate cancer, LNCaP cells were 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. Treatment with 100 µm NS398 caused a down-regulation in bcl-2 protein expression, followed by chromatin condensation, chromosomal DNA fragmentation, and changes in nuclear morphology detected by 4,6-diamidino-2-phenylindole staining, DNA fragmentation assay, and terminal deoxynucleotidyl transferase-mediated UTP-biotin nick end-labeling assay. In contrast, NS398 treatment had no effect on either cell viability or nuclear function and morphology in human fetal prostate fibroblasts. These results demonstrate that NS398 induces apoptosis in LNCaP cells but not in human fetal prostate fibroblasts, and that this induction is associated with a decreased level of bcl-2 protein.
↵1 This work was supported by grants-in-aid from the T.J. Martell Foundation for Leukemia, Cancer, and AIDS Research.
↵2 To whom requests for reprints should be addressed, at Department of Urology, Box 1272, Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY 10029. Phone: (212) 241-4130; Fax: (212) 241-4218.
- Received June 26, 1998.
- Accepted August 17, 1998.
- ©1998 American Association for Cancer Research.