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

文献类型：期刊论文

作者Kuang, Shan1,2; Liu, Ge1,2,3; Cao, Ruobing1,2,3; Zhang, Linlin1,2,3; Yu, Qiang4; Sun, Chaomin1,2
刊名ONCOTARGET
出版日期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
DOI10.18632/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
资助项目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[00000000] ; "100-Talent Project" of Chinese Academy of Sciences[00000000] ; Special Fund for Postdoctoral Innovation Project of Shandong Province[201502032] ; Qingdao Postdoctoral Application Research[00000000] ; AoShan Talents Program[00000000]
WOS研究方向Oncology ; Cell Biology
语种英语
WOS记录号WOS:000419562500104
出版者IMPACT JOURNALS LLC
源URL[http://119.78.100.183/handle/2S10ELR8/272390]  
专题药理学第一研究室
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.

入库方式： OAI收割

来源：上海药物研究所

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