Apoptosis in human oral squamous cell carcinomas is induced by 15-deoxy-delta 12,14-prostaglandin J2 but not by troglitazone.
15-deoxy-Delta(12,14)-prostaglandin J(2) (15-d-PGJ(2)) 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-gamma 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-PGJ(2) or troglitazone decreased cell viability in a time- and dose-dependent manner. 15-d-PGJ(2), but not troglitazone, induced apoptosis, and this effect was time-dependent. Exposure of cells to 20 micro M of 15-d-PGJ(2) 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 micro M of 15-d-PGJ(2) blocked apoptosis. Our study demonstrates that treatment with 15-d-PGJ(2), but not troglitazone, induces apoptosis in human SCC cell lines, and 15-d-PGJ(2) appears to work through cytochrome c release and caspase activation.
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000008:administration & dosage / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003574:Cytochrome c Group / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology*; D009062:Mouth Neoplasms / Q000473:pathology*; D009842:Oligopeptides / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D045162:Thiazolidinediones; D013997:Time Factors; D000077288:Troglitazone; D014407:Tumor Cells, Cultured
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000590:Amino Acid Chloromethyl Ketones; D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D002839:Chromans; D015853:Cysteine Proteinase Inhibitors; D003574:Cytochrome c Group; D007155:Immunologic Factors; D009842:Oligopeptides; D013844:Thiazoles; D045162:Thiazolidinediones; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D020169:Caspases; D000077288:Troglitazone; D015230:Prostaglandin D2