Knowledge Management System of Northwest Institute of Plateau Biology, CAS
| MMPT as a reactive oxygen species generator induces apoptosis via the depletion of intracellular GSH contents in A549 cells | |
| Zhao, Yun-feng1,2; Zhang, Cui3; Suo, You-rui2 | |
| 2012-08-05 | |
| 发表期刊 | EUROPEAN JOURNAL OF PHARMACOLOGY
 |
| ISSN | 0014-2999 |
| 卷号 | 688期号:1-3页码:6-13 |
| 文章类型 | Article |
| 摘要 | MMPT, (5-[(4-methylphenyl) methylene]-2-(phenylamino)-4(5H)-thiazolone), a thiazolidin compound, was identified in our laboratory as a novel antineoplastic agent with a broad spectrum of antitumor activity against many human cancer cells. A previous study showed that MMPT inhibited cell growth, and induced apoptosis in H1792 cells. In this study, the antiproliferative activity of MMPT was investigated. The results showed that MMPT was able to inhibit A549 cell growth in a time-and dose-dependent manner by blocking cell cycle progression in the G2 phase and inducing apoptosis. MMPT induced DNA fragmentation and caspase activation in A549 cells, both of which are hallmarks of apoptosis. The apoptotic process was accompanied by the generation of reactive oxygen species, depletion of glutathione (GSH), and reduction the GSH/GSSG ratio, suggesting that MMPT may induce apoptosis in A549 cells through a reactive oxygen species dependent pathway. Treatment with a thiol antioxidant, NAC, showed the recovery of GSH depletion and the reduction of reactive oxygen species levels in MMPT-treated cells, which were accompanied by the inhibition of apoptosis. In contrast, L-buthionine sulfoximine (BSO), a well-known inhibitor of GSH synthesis, aggravated GSH depletion and cell death in MMPT-treated cells. In conclusion, we have demonstrated that MMPT inhibits the growth of A549 cells by inducing a G2 arrest of the cell cycle and by triggering apoptosis accompanied with the depletion of GSH. (C) 2012 Elsevier B.V. All rights reserved.; MMPT, (5-[(4-methylphenyl) methylene]-2-(phenylamino)-4(5H)-thiazolone), a thiazolidin compound, was identified in our laboratory as a novel antineoplastic agent with a broad spectrum of antitumor activity against many human cancer cells. A previous study showed that MMPT inhibited cell growth, and induced apoptosis in H1792 cells. In this study, the antiproliferative activity of MMPT was investigated. The results showed that MMPT was able to inhibit A549 cell growth in a time-and dose-dependent manner by blocking cell cycle progression in the G2 phase and inducing apoptosis. MMPT induced DNA fragmentation and caspase activation in A549 cells, both of which are hallmarks of apoptosis. The apoptotic process was accompanied by the generation of reactive oxygen species, depletion of glutathione (GSH), and reduction the GSH/GSSG ratio, suggesting that MMPT may induce apoptosis in A549 cells through a reactive oxygen species dependent pathway. Treatment with a thiol antioxidant, NAC, showed the recovery of GSH depletion and the reduction of reactive oxygen species levels in MMPT-treated cells, which were accompanied by the inhibition of apoptosis. In contrast, L-buthionine sulfoximine (BSO), a well-known inhibitor of GSH synthesis, aggravated GSH depletion and cell death in MMPT-treated cells. In conclusion, we have demonstrated that MMPT inhibits the growth of A549 cells by inducing a G2 arrest of the cell cycle and by triggering apoptosis accompanied with the depletion of GSH. (C) 2012 Elsevier B.V. All rights reserved. |
| 关键词 | A549 Cells Apoptosis Caspase Gsh Mmpt Reactive Oxygen Species |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 关键词[WOS] | ENDOPLASMIC-RETICULUM STRESS ; PANCREATIC-CANCER CELLS ; OXIDATIVE STRESS ; MITOCHONDRIAL ; GLUTATHIONE ; ANTIOXIDANT ; ACTIVATION ; CASPASES ; GROWTH ; INDUCTION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS研究方向 | Pharmacology & Pharmacy |
| WOS类目 | Pharmacology & Pharmacy |
| WOS记录号 | WOS:000306106800002 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://210.75.249.4/handle/363003/3624 |
| 专题 | 中国科学院西北高原生物研究所 |
| 作者单位 | 1.Qufu Normal Univ, Sch Life Sci, Qufu 273165, Shandong, Peoples R China 2.Chinese Acad Sci, NW Inst Plateau Biol, Xining 810008, Peoples R China 3.Taishan Univ, Dept Biol Sci & Technol, Tai An 271021, Shandong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhao, Yun-feng,Zhang, Cui,Suo, You-rui. MMPT as a reactive oxygen species generator induces apoptosis via the depletion of intracellular GSH contents in A549 cells[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2012,688(1-3):6-13. |
| APA | Zhao, Yun-feng,Zhang, Cui,&Suo, You-rui.(2012).MMPT as a reactive oxygen species generator induces apoptosis via the depletion of intracellular GSH contents in A549 cells.EUROPEAN JOURNAL OF PHARMACOLOGY,688(1-3),6-13. |
| MLA | Zhao, Yun-feng,et al."MMPT as a reactive oxygen species generator induces apoptosis via the depletion of intracellular GSH contents in A549 cells".EUROPEAN JOURNAL OF PHARMACOLOGY 688.1-3(2012):6-13. |
| 条目包含的文件 | 下载所有文件 | |||||
| 文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 | ||
| MMPT as a reactive o（1085KB） | 开放获取 | -- | 浏览 下载 | |||
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。
修改评论