15-deoxy-Δ12,14-prostaglandin J2 (15-d-PGJ2) and troglitazone have been shown to induce apoptosis in several carcinoma cell lines. However, apoptotic signaling pathways of these agents are poorly understood. We tested the hypothesis that peroxisome proliferator-activated receptor-γ ligands such as these two agents will induce caspase-mediated apoptosis in human oral squamous cell carcinomas (SCC). Treatment of these cell lines with 15-d-PGJ2 or troglitazone decreased cell viability in a time- and dose-dependent manner. 15-d-PGJ2, but not troglitazone, induced apoptosis, and this effect was time-dependent. Exposure of cells to 20 μM of 15-d-PGJ2 initiated early cytochrome c release, followed by late caspase activation. Furthermore, co-treatment with caspase inhibitors such as Z-VAD-FMK or Z-DEVD-FMK of oral SCC cells that had been treated with 20 μM of 15-d-PGJ2 blocked apoptosis. Our study demonstrates that treatment with 15-d-PGJ2, but not troglitazone, induces apoptosis in human SCC cell lines, and 15-d-PGJ2 appears to work through cytochrome c release and caspase activation.
Comparison of DNA Copy Numbers in Original Oral Squamous Cell Carcinomas and Corresponding Cell Lines by Comparative Genomic Hybridization