Apoptosis in Human Oral Squamous Cell Carcinomas is Induced by 15-Deoxy-Δ 12,14 -Prostaglandin J 2 but not by Troglitazone

Abstract

15-deoxy-Δ^12,14-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.

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