MMPT as a reactive oxygen species generator induces apoptosis via the depletion of intracellular GSH contents in A549 cells

NWIPB OpenIR

	MMPT as a reactive oxygen species generator induces apoptosis via the depletion of intracellular GSH contents in A549 cells
	Zhao, Yun-feng ; Zhang, Cui ; Suo, You-rui
	2012-08-05
发表期刊	EUROPEAN JOURNAL OF PHARMACOLOGY ; Chen, G; Li, J; Zhang, SJ; Song, CH; Li, GL; Sun, ZW; Suo, YR; You, JM.MMPT as a reactive oxygen species generator induces apoptosis via the depletion of intracellular GSH contents in A549 cells,EUROPEAN JOURNAL OF PHARMACOLOGY,2012,688(1-3 ):6-13
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.
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/26667
专题	中国科学院西北高原生物研究所
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, Chen, G; Li, J; Zhang, SJ; Song, CH; Li, GL; Sun, ZW; Suo, YR; You, JM.MMPT as a reactive oxygen species generator induces apoptosis via the depletion of intracellular GSH contents in A549 cells,EUROPEAN JOURNAL OF PHARMACOLOGY,2012,688(1-3 ):6-13,2012.
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.
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 (2012).