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Disulfiram chelated with copper promotes apoptosis in human breast cancer cells by impairing the mitochondria functions

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机构: [1]Analysis and Test Center, Jinan University, Guangzhou, China [2]Department of Pharmacology, Medical College, Jinan University, Guangzhou, China [3]Department of Physiology, Medical College, Jinan University, Guangzhou, China [4]Department of Pathology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
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关键词: disulfiram-Cu complex atomic force microscopy cytoskeleton reactive oxygen species mitochondrial membrane potential

摘要:
Disulfiram (DSF) has been proved to have broad-spectrum anti-alcoholism effects, and it is also found to show stronger anti-tumor effects after chelating with Cu2+ to form DSF-Cu complex. In this work, we studied the anti-tumor activity of DSF-Cu in MCF-7 cells by flow cytometry, confocal laser scanning microscope, and atomic force microscopy to clarify the underlying anti-tumor mechanisms. MCF-7 cells were incubated with 50, 100, 150, 200, and 250nM DSF chelated with 10 mu M CuCl2 for 24h. The results showed that DSF-Cu could induce the accumulation of MCF-7 cells in G2/M phase and apoptosis in a concentration-dependent manner. Additionally, atomic force microscope (AFM) analysis at nanoscale level showed that the morphology of cell was significantly shrunk with destroyed filopodia and ultrastructure presented many irregular protuberances on the cell membrane after DSF-Cu treatment, which was closely associated with the re-arrangement of cytoskeleton. DSF-Cu induced the production of reactive oxygen species (ROS), increased the concentration of intracellular Ca2+ and decreased the mitochondrial membrane potential (MMP) in MCF-7 cells resulting in a mitochondria-dependent apoptosis pathway. The results indicated that DSF-Cu has a potential anti-tumor activity in breast cancer by impairing the mitochondria functions. SCANNING 38:825-836, 2016. (c) 2016 Wiley Periodicals, Inc.

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出版当年[2015]版:
大类 | 3 区 工程技术
小类 | 3 区 仪器仪表 4 区 显微镜技术
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Q2 MICROSCOPY Q2 INSTRUMENTS & INSTRUMENTATION
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第一作者机构: [1]Analysis and Test Center, Jinan University, Guangzhou, China
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通讯机构: [2]Department of Pharmacology, Medical College, Jinan University, Guangzhou, China [4]Department of Pathology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China [*1]Department of Pathology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510120, China [*2]Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China
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