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Molecular study on copper-mediated tumor proteasome inhibition and cell death
Xiao, Yan1,2,3,4; Chen, Di1,2; Zhang, Xia1,2,3; Cui, Qiuzhi1,2; Fan, Yuhua3; Bi, Caifeng3; Dou, Q. Ping1,2
2010-07-01
发表期刊INTERNATIONAL JOURNAL OF ONCOLOGY
卷号37期号:1页码:81-87
摘要The metal ion copper is a cofactor essential for maintaining normal biological and physical functions in human beings. High copper levels have been found in variety of tumor tissues and are involved in tumor angiogenesis processes. The ubiquitin-proteasome system plays an important role in cell growth and apoptosis and has been shown as a novel target for cancer therapy. We previously reported that some organic copper complexes can inhibit the proteasomal chymotrypsin-like activity and induce apoptosis in human cancer cells and xenograft models. In the current study, we investigated the effect of oxidation status of copper, Cu(I) or Cu(II), on inhibition of proteasome activity, induction of apoptosis, and induction of reactive oxygen species (ROS) in human cancer cells. We report four major findings here: i) both Cu(I) and Cu(II) could inhibit the chymotrypsin-like activity of purified 20S proteasome, but Cu(I) was more potent than Cu(H), ii) purified 20S proteasome protein was able to reduce Cu(II) to Cu(I), suggesting that Cu(I) is the oxidation status of copper that directly reacts with the proteasome, iii) when complexed with the copper ligand neocuproine, Cu(I) showed higher ability to induce ROS production in cancer cells, compared with Cu(II), iv) addition of a ROS scavenger in the cancer cell culture-blocked copper-induced ROS generation, but did not overcome copper-mediated proteasome-inhibitory and cell death-inducing events, demonstrating the ROS-independent proteasome-inhibitory property of copper complexes.
文章类型Article
关键词Copper Oxidation Status Proteasome Inhibition Apoptosis Ros
WOS标题词Science & Technology ; Life Sciences & Biomedicine
DOI10.3892/ijo_00000655
关键词[WOS]OXIDATIVE STRESS ; TRACE-ELEMENTS ; BREAST-CANCER ; APOPTOSIS ; ANGIOGENESIS ; NEOCUPROINE ; XENOGRAFTS ; ACTIVATION ; INDUCTION ; COMPLEX
收录类别SCI
语种英语
WOS研究方向Oncology
WOS类目Oncology
WOS记录号WOS:000279135000010
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被引频次:48[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/337004/6529
专题代谢物组学研究组
作者单位1.Wayne State Univ, Prevent Program, Barbara Ann Karmanos Canc Inst, Sch Med, Detroit, MI 48201 USA
2.Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA
3.Ocean Univ China, Coll Chem & Chem Engn, Minist Educ, Key Lab Marine Chem Engn & Technol, Qingdao 266101, Peoples R China
4.Chinese Acad Sci, Qingdao Inst Bioenergy & Bioproc Technol, Qingdao 266101, Peoples R China
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Xiao, Yan,Chen, Di,Zhang, Xia,et al. Molecular study on copper-mediated tumor proteasome inhibition and cell death[J]. INTERNATIONAL JOURNAL OF ONCOLOGY,2010,37(1):81-87.
APA Xiao, Yan.,Chen, Di.,Zhang, Xia.,Cui, Qiuzhi.,Fan, Yuhua.,...&Dou, Q. Ping.(2010).Molecular study on copper-mediated tumor proteasome inhibition and cell death.INTERNATIONAL JOURNAL OF ONCOLOGY,37(1),81-87.
MLA Xiao, Yan,et al."Molecular study on copper-mediated tumor proteasome inhibition and cell death".INTERNATIONAL JOURNAL OF ONCOLOGY 37.1(2010):81-87.
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