title: Disulfiram chelated with copper promotes apoptosis in human breast cancer cells by impairing the mitochondria functions.
abstract: 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 250 nM DSF chelated with 10 µM CuCl2for 24 h. 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. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Analysis and Test Center, Jinan University, Guangzhou, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Kefan
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Mengjia
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Sun
authors.affiliation: Analysis and Test Center, Jinan University, Guangzhou, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pathology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Linyan
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism; D003300:Copper / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects; D004221:Disulfiram / Q000494:pharmacology*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D018625:Microscopy, Atomic Force; D008928:Mitochondria / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D003300:Copper; D002118:Calcium; D004221:Disulfiram
keywords: atomic force microscopy; cytoskeleton; disulfiram-Cu complex; mitochondrial membrane potential; reactive oxygen species