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.
Chen
Shu-Yi
SY
Graduated Institute (Department) of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan, ROC.
Lu
Fung-Jou
FJ
Gau
Rung-Jiun
RJ
Yang
Mei-Ling
ML
Huang
Tien-Shang
TS
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