15-deoxy-Δ12,14-prostaglandin J2 induces apoptosis of a thyroid papillary cancer cell line (CG3 cells) through increasing intracellular iron and oxidative stress

15-deoxy-Δ12,14-prostaglandin J2 induces apoptosis of a thyroid papillary cancer cell line (CG3 cells) through increasing intracellular iron and oxidative stress
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DOI:
10.1097/00001813-200208000-00011
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发表时间:
2002-08-01
期刊:
影响因子:
2.3
通讯作者:
Huang, TS
Huang, TS
中科院分区:
医学4区
文献类型:
--
作者:
Chen, SY;Lu, FJ;Huang, TS

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据报道,15-脱氧-三角洲(12,14)-前列腺素J(2)(15d-PGJ(2))是过氧化体增殖物激活受体-γ的天然配体,可以诱导细胞凋亡和/或抑制细胞增殖。在本研究中,我们研究了15d-PGJ2对甲状腺乳头状癌细胞系CG3的细胞毒作用及其机制。结果表明,15d-PGJ2具有细胞毒性作用,细胞内ROS含量增加。线粒体氧化磷酸化抑制剂(羰基氰化物、间氯苯肼、寡霉素、环孢菌素A和鱼藤酮)、NADPH氧化酶抑制剂(二苯基碘)、黄嘌呤氧化酶抑制剂(别嘌醇)和一氧化氮合酶抑制剂(N-单甲基-L-精氨酸乙酸酯)不能减少ROS的产生。然而,过氧化氢酶、N-乙酰半胱氨酸和铁络合剂去铁胺降低了15d-PGJ(2)处理的CG3细胞内ROS。此外,15d-PGJ2促进了CG3细胞中铁的积累。这些数据表明,15d-PGJ2通过促进细胞内铁的积累来诱导ROS的产生,而氧化应激的增加可能导致CG3细胞的凋亡。[(C)2002年利平科特·威廉姆斯·威尔金斯。]。
Treatment of carcinoma cell lines with 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), 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-chlorophenylhydrazone, 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 desferrioxamine decreased the intracellular ROS of 15d-PGJ(2)-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. [(C) 2002 Lippincott Williams Wilkins.].