15-Deoxy-delta12,14-prostaglandin J2 induces apoptosis of a thyroid papillary cancer cell line (CG3 cells) through increasing intracellular iron and oxidative stress.
Treatment of carcinoma cell lines with 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2), a natural ligand of the peroxisome proliferator-activated receptor-gamma, has been reported to induce apoptosis and/or inhibit proliferation. In this study, we investigated the cytotoxic effect and the action mechanisms of 15d-PGJ2 in a thyroid papillary cancer cell line, CG3. The results indicate that 15d-PGJ2 caused cytotoxicity and increased the amount of intracellular reactive oxygen species (ROS) in these cells. Mitochondrial oxidative phosphorylation inhibitors (carbonyl cyanide m-chloro-phenylhydrazone, oligomycin, cyclosporin A and rotenone), NADPH oxidase inhibitor (diphenyleneiodonium), xanthine oxidase inhibitor (allopurinol) and NO synthase inhibitor (N-monomethyl-L-arginine acetate) did not reduce the generation of ROS. However, catalase, N-acetyl-cysteine and the iron chelator desferri-oxamine decreased the intracellular ROS of 15d-PGJ2-treated CG3 cells. Furthermore, 15d-PGJ2 enhanced the accumulation of iron in the CG3 cells. These data suggest that 15d-PGJ2 induces the generation of ROS by enhancing the accumulation of intracellular iron and that the increased oxidative stress may cause apoptosis of CG3 cells.
Graduated Institute (Department) of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan, ROC.
Shu-Yi
SY
Chen
Fung-Jou
FJ
Lu
Rung-Jiun
RJ
Gau
Mei-Ling
ML
Yang
Tien-Shang
TS
Huang
D017209:Apoptosis / Q000187:drug effects*; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007202:Indicators and Reagents; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013268:Stimulation, Chemical; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D007155:Immunologic Factors; D007202:Indicators and Reagents; D007502:Iron Chelating Agents; D017382:Reactive Oxygen Species; D007501:Iron; D020169:Caspases; D015230:Prostaglandin D2