Mansouramycin C kills cancer cells through reactive oxygen species production mediated by opening of mitochondrial permeability transition pore

doi:10.18632/oncotarget.22004

	Mansouramycin C kills cancer cells through reactive oxygen species production mediated by opening of mitochondrial permeability transition pore
	Kuang, Shan 1,2; Liu, Ge 1,2,3; Cao, Ruobing 1,2,3; Zhang, Linlin 1,2,3; Yu, Qiang 4; Sun, Chaomin 1,2
刊名	ONCOTARGET
	2017-11-28
卷号	8 期号:61 页码:104057-104071
关键词	Mansouramycin c Marine-derived Isoquinolinequinone Reactive Oxygen Species Mitochondrial Permeability Transition Pore Anticancer Drug
ISSN号	1949-2553
DOI	10.18632/oncotarget.22004
文献子类	Article
英文摘要	Cancer is one of the deadliest diseases in the world and the search for novel anticancer agents is urgently required. Marine-derived isoquinolinequinones have exhibited promising anticancer activities. However, the exact mechanisms of cytotoxic activities of these isoquinolinequinones are poorly characterized. In this study, we investigated the anticancer effects and molecular mechanisms of mansouramycin C (Mm C), a cytotoxic isoquinolinequinone isolated from a marine streptomycete. We demonstrated that Mm C preferentially killed cancer cells and the cytotoxic effects were mediated by reactive oxygen species (ROS) generation. Mass spectrometry based proteomic analysis of Mm C-treated A549 cells revealed that many ROS-related proteins were differentially expressed. Proteomic-profiling after Mm C treatment identified oxidative phosphorylation as the most significant changes in pathways. Analysis also revealed extensive defects in mitochondrial structure and function. Furthermore, we disclosed that Mm C-induced ROS generation was caused by opening of mitochondrial permeability transition pore. Notably, Mm C synergized with sorafenib to induce cell death in A549 cells. Hence, we propose that the marine-derived natural compound Mm C is a potent inducer of the mitochondrial permeability transition and a promising anticancer drug candidate. Moreover, molecular mechanisms of Mm C shed new light on the understanding of the cytotoxic mechanisms of marine-derived isoquinolinequiones.
WOS关键词	STRESS-INDUCED APOPTOSIS ; OXIDATIVE STRESS ; HYDROGEN-PEROXIDE ; CYCLOSPORINE-A ; ROS ; DEATH ; MEMBRANE ; OPPORTUNITIES ; INHIBITION ; MECHANISMS
WOS研究方向	Oncology ; Cell Biology
语种	英语
出版者	IMPACT JOURNALS LLC
WOS记录号	WOS:000419562500104
资助机构	Qingdao National Laboratory for Marine Science and Technology(2015ASTP) ; Natural Science Outstanding Youth Fund of Shandong Province(JQ201607) ; Taishan Young Scholar Program of Shandong Province ; "100-Talent Project" of Chinese Academy of Sciences ; Special Fund for Postdoctoral Innovation Project of Shandong Province(201502032) ; Qingdao Postdoctoral Application Research ; AoShan Talents Program
内容类型	期刊论文
源URL	[http://ir.qibebt.ac.cn/handle/337004/10573]
专题	中国科学院青岛生物能源与过程研究所
通讯作者	Sun, Chaomin
作者单位	1.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao, Peoples R China 2.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Biol & Biotechnol, Qingdao, Peoples R China 3.Univ Chinese Acad Sci, Coll Earth Sci, Beijing, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Div Tumor Pharmacol, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Kuang, Shan,Liu, Ge,Cao, Ruobing,et al. Mansouramycin C kills cancer cells through reactive oxygen species production mediated by opening of mitochondrial permeability transition pore[J]. ONCOTARGET,2017,8(61):104057-104071.
APA	Kuang, Shan,Liu, Ge,Cao, Ruobing,Zhang, Linlin,Yu, Qiang,&Sun, Chaomin.(2017).Mansouramycin C kills cancer cells through reactive oxygen species production mediated by opening of mitochondrial permeability transition pore.ONCOTARGET,8(61),104057-104071.
MLA	Kuang, Shan,et al."Mansouramycin C kills cancer cells through reactive oxygen species production mediated by opening of mitochondrial permeability transition pore".ONCOTARGET 8.61(2017):104057-104071.