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

doi:10.18632/oncotarget.22004

QIBEBT-IR

	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
	2017-11-28
发表期刊	ONCOTARGET
ISSN	1949-2553
卷号	8 期号:61 页码:104057-104071
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.
文章类型	Article
关键词	Mansouramycin c Marine-derived Isoquinolinequinone Reactive Oxygen Species Mitochondrial Permeability Transition Pore Anticancer Drug
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
DOI	10.18632/oncotarget.22004
关键词[WOS]	STRESS-INDUCED APOPTOSIS ; OXIDATIVE STRESS ; HYDROGEN-PEROXIDE ; CYCLOSPORINE-A ; ROS ; DEATH ; MEMBRANE ; OPPORTUNITIES ; INHIBITION ; MECHANISMS
收录类别	SCI
语种	英语
WOS研究方向	Oncology ; Cell Biology
项目资助者	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
WOS类目	Oncology ; Cell Biology
WOS记录号	WOS:000419562500104
出版者	IMPACT JOURNALS LLC
引用统计	被引频次：14[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.qibebt.ac.cn/handle/337004/10574
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.