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disulfiram copper

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https://www.readbyqxmd.com/read/27894956/disulfiram-induces-anoikis-and-suppresses-lung-colonization-in-triple-negative-breast-cancer-via-calpain-activation
#1
Ji Young Kim, Nahyun Lee, Yoon-Jae Kim, Youngkwan Cho, Hyunsook An, Eunhye Oh, Tae-Min Cho, Daeil Sung, Jae Hong Seo
Triple-negative breast cancers (TNBC) often exhibit an aggressive phenotype. Disulfiram (DSF) is an approved drug for the treatment of alcohol dependence, but has also been shown to kill TNBC cells in a copper (Cu)-dependent manner. Exactly how this occurs has not been clearly elucidated. We sought to investigate the mechanisms responsible for DSF/Cu-dependent induction of apoptosis and suppression of lung colonization by TNBC cells. DSF/Cu induced anoikis and significantly suppressed cell migration and invasion with negative effects on focal adhesions, coinciding with vimentin breakdown and calpain activation in TNBC cells...
November 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27793743/dopamine-beta-hydroxylase-participate-in-the-immunoendocrine-responses-of-hypothermal-stressed-white-shrimp-litopenaeus-vannamei
#2
Winton Cheng, Ya-Wen Ka, Chin-Chyuan Chang
Dopamine beta-hydroxylase (DBH) plays a critical role in catecholamine (CA) synthesis of neuroendocrine regulatory network, and is suggested to be involved in the immunoendocrine responses of invertebrate against bacterial challenge. DBH has been identified in white shrimp, Litopenaeus vannamei, and further investigation on its potential function was conducted after hypothermal stress, pharmaceutical inhibition and gene silencing in the present study. Cloned DBH L. vannamei (LvDBH), belonging to the Copper type II, ascorbate-dependent monooxygenases, was characterized by a DOMON domain, a Cu2_monooxygen domain and three glycosylation sites, and its expression was abundant in thoracic ganglia and haemocytes determined by quantitative real-time PCR...
December 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27708770/the-cytotoxic-mechanisms-of-disulfiram-and-copper-ii-in-cancer-cells
#3
Patricia Erebi Tawari, Zhipeng Wang, Mohammad Najlah, Chi Wai Tsang, Vinodh Kannappan, Peng Liu, Christopher McConville, Bin He, Angel L Armesilla, Weiguang Wang
The anticancer activity of disulfiram (DS) is copper(ii) (Cu)-dependent. This study investigated the anticancer mechanisms of DS/Cu using in vitro cytotoxicity and metabolic kinetic analysis. Our study indicates that DS/Cu targets cancer cells by the combination of two types of actions: (1) instant killing executed by DS/Cu reaction generated reactive oxygen species; (2) delayed cytotoxicity introduced by the end product, DDC-Cu. Nanoencapsulation of DS might shed light on repositioning of DS into cancer treatment...
November 19, 2015: Toxicology Research
https://www.readbyqxmd.com/read/27542268/targeting-aldh1a1-by-disulfiram-copper-complex-inhibits-non-small-cell-lung-cancer-recurrence-driven-by-aldh-positive-cancer-stem-cells
#4
Xinwei Liu, Lihui Wang, Wei Cui, Xiangzhong Yuan, Lulu Lin, Qi Cao, Nannan Wang, Yi Li, Wei Guo, Xun Zhang, Chunfu Wu, Jingyu Yang
The existence of cancer stem cells (CSCs) in non-small cell lung cancer (NSCLC) has profound implications for cancer therapy. In this study, a disulfiram/copper (DSF/Cu) complex was evaluated in vitro and in vivo for its efficacy to inhibit CSCs, which drive recurrence of NSCLC. First, we investigated whether DSF/Cu could inhibit ALDH-positive NSCLC stem cells in vitro and tumors derived from sorted ALDH-positive CSCs in vivo. DSF/Cu (0.5/1 μmol/l) significantly inhibited the expression of stem cell transcription factors (Sox2, Oct-4 and Nanog) and reduced the capacities of NSCLC stem cells for self-renewal, proliferation and invasion in vitro...
August 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27521693/poly-lactic-co-glycolic-acid-controlled-delivery-of-disulfiram-to-target-liver-cancer-stem-like-cells
#5
Zhipeng Wang, Jiao Tan, Christopher McConville, Vinodh Kannappan, Patricia Erebi Tawari, James Brown, Jin Ding, Angel L Armesilla, Juan M Irache, Qi-Bing Mei, Yuhuan Tan, Ying Liu, Wenguo Jiang, Xiuwu Bian, Weiguang Wang
Disulfiram (DS), an anti-alcoholism drug, shows very strong cytotoxicity in many cancer types. However its clinical application in cancer treatment is limited by the very short half-life in the bloodstream. In this study, we developed a poly lactic-co-glycolic acid (PLGA)-encapsulated DS protecting DS from the degradation in the bloodstream. The newly developed DS-PLGA was characterized. The DS-PLGA has very satisfactory encapsulation efficiency, drug-loading content and controlled release rate in vitro. PLGA encapsulation extended the half-life of DS from shorter than 2minutes to 7hours in serum...
August 10, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27414036/the-comparative-effects-of-diethyldithiocarbamate-copper-complex-with-established-proteasome-inhibitors-on-expression-levels-of-cyp1a2-3a4-and-their-master-regulators-aryl-hydrocarbon-and-pregnane-x-receptor-in-primary-cultures-of-human-hepatocytes
#6
Radim Vrzal, Zdenek Dvorak
In the recent years, a therapeutic potential of disulfiram (Antabuse) complex with copper, as an anticancer drug, was recognized towards several cancer cell lines. The proteasome was suggested as one of the cellular targets for this compound. As the therapeutic use of diethyldithiocarbamate-copper complex (CuET) is expected to increase, it is of great interest to know whether this compound may be the source of drug-drug interactions via the induction of biotransformation enzymes, especially cytochromes P450 (CYPs)...
December 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27353661/disulfiram-chelated-with-copper-promotes-apoptosis-in-human-breast-cancer-cells-by-impairing-the-mitochondria-functions
#7
Yaping Yang, Kefan Zhang, Yawei Wang, Mengjia Li, Xiaoxue Sun, Zhihong Liang, Liwei Wang, Lixin Chen, Haifeng Yang, Linyan Zhu
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 Cu(2+) 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 CuCl2 for 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...
June 29, 2016: Scanning
https://www.readbyqxmd.com/read/27259232/characterization-and-use-of-hapt1-derived-homologous-tumors-as-a-preclinical-model-to-evaluate-therapeutic-efficacy-of-drugs-against-pancreatic-tumor-desmoplasia
#8
Sujit Suklabaidya, Biswajit Das, Syed Azmal Ali, Sumeet Jain, Sharada Swaminathan, Ashok K Mohanty, Susen K Panda, Pujarini Dash, Subhankar Chakraborty, Surinder K Batra, Shantibhusan Senapati
Desmoplasia in human pancreatic cancer (PC) promotes cancer progression and hinders effective drug delivery. The objectives of this study were to characterize a homologous orthotopic model of PC in Syrian golden hamster and investigate the effect of anti-fibrotic (pirfenidone), antioxidant (N-acetyl cysteine, NAC) and anti-addiction (disulfiram, DSF) drugs on desmoplasia and tumor growth in this model. The HapT1 PC cells when implanted orthotopically into hamsters formed tumors with morphological, cellular and molecular similarities to human PC...
July 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27238567/disulfiram-targets-cancer-stem-like-properties-and-the-her2-akt-signaling-pathway-in-her2-positive-breast-cancer
#9
Ji Young Kim, Youngkwan Cho, Eunhye Oh, Nahyun Lee, Hyunsook An, Daeil Sung, Tae-Min Cho, Jae Hong Seo
HER2-positive breast tumors are known to harbor cancer stem-like cell populations and are associated with an aggressive tumor phenotype and poor clinical outcomes. Disulfiram (DSF), an anti-alcoholism drug, is known to elicit cytotoxicity in many cancer cell types in the presence of copper (Cu). The objective of the present study was to investigate the mechanism of action responsible for the induction of apoptosis by DSF/Cu and its effect on cancer stem cell properties in HER2-positive breast cancers in vitro and in vivo...
August 28, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27203215/effective-elimination-of-adult-b-lineage-acute-lymphoblastic-leukemia-by-disulfiram-copper-complex-in-vitro-and-in-vivo-in-patient-derived-xenograft-models
#10
Manman Deng, Zhiwu Jiang, Yin Li, Yong Zhou, Jie Li, Xiangmeng Wang, Yao Yao, Weiguang Wang, Peng Li, Bing Xu
Disulfiram (DS), a clinically used drug to control alcoholism, has displayed promising anti-cancer activity against a wide range of tumors. Here, we demonstrated that DS/copper (Cu) complex effectively eliminated adult B-ALL cells in vitro and in vivo in patient-derived xenograft (PDX) humanized mouse models, reflected by inhibition of cell proliferation, induction of apoptosis, suppression of colony formation, and reduction of PDX tumor growth, while sparing normal peripheral blood mononuclear cells. Mechanistically, these events were associated with disruption of mitochondrial membrane potential and down-regulation of the anti-apoptotic proteins Bcl-2 and Bcl-xL...
May 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27175597/copper-as-a-target-for-prostate-cancer-therapeutics-copper-ionophore-pharmacology-and-altering-systemic-copper-distribution
#11
Delphine Denoyer, Helen B Pearson, Sharnel A S Clatworthy, Zoe M Smith, Paul S Francis, Roxana M Llanos, Irene Volitakis, Wayne A Phillips, Peter M Meggyesy, Shashank Masaldan, Michael A Cater
Copper-ionophores that elevate intracellular bioavailable copper display significant therapeutic utility against prostate cancer cells in vitro and in TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice. However, the pharmacological basis for their anticancer activity remains unclear, despite impending clinical trails. Herein we show that intracellular copper levels in prostate cancer, evaluated in vitro and across disease progression in TRAMP mice, were not correlative with copper-ionophore activity and mirrored the normal levels observed in patient prostatectomy tissues (Gleason Score 7 & 9)...
June 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27139157/preliminary-evaluation-of-prostate-targeted-radiotherapy-using-131-i-mip-1095-in-combination-with-radiosensitising-chemotherapeutic-drugs
#12
Mathias Tesson, Colin Rae, Colin Nixon, John W Babich, Robert J Mairs
OBJECTIVES: Despite recent advances in the treatment of metastatic prostate cancer, survival rates are low and treatment options are limited to chemotherapy and hormonal therapy. (131) I-MIP-1095 is a recently developed prostate-specific membrane antigen (PSMA)-targeting, small molecular weight radiopharmaceutical which has anti-tumour activity as a single agent. Our purpose was to determine in vitro the potential benefit to be gained by combining (131) I-MIP-1095 with cytotoxic drug treatments...
July 2016: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27055237/nanoscale-reaction-vessels-designed-for-synthesis-of-copper-drug-complexes-suitable-for-preclinical-development
#13
Mohamed Wehbe, Malathi Anantha, Ian Backstrom, Ada Leung, Kent Chen, Armaan Malhotra, Katarina Edwards, Marcel B Bally
The development of copper-drug complexes (CDCs) is hindered due to their very poor aqueous solubility. Diethyldithiocarbamate (DDC) is the primary metabolite of disulfiram, an approved drug for alcoholism that is being repurposed for cancer. The anticancer activity of DDC is dependent on complexation with copper to form copper bis-diethyldithiocarbamate (Cu(DDC)2), a highly insoluble complex that has not been possible to develop for indications requiring parenteral administration. We have resolved this issue by synthesizing Cu(DDC)2 inside liposomes...
2016: PloS One
https://www.readbyqxmd.com/read/27006494/disulfiram-when-combined-with-copper-enhances-the-therapeutic-effects-of-temozolomide-for-the-treatment-of-glioblastoma
#14
Xueqing Lun, J Connor Wells, Natalie Grinshtein, Jennifer C King, Xiaoguang Hao, Ngoc-Ha Dang, Xiuling Wang, Ahmed Aman, David Uehling, Alessandro Datti, Jeffrey L Wrana, Jacob C Easaw, Artee Luchman, Samuel Weiss, J Gregory Cairncross, David R Kaplan, Stephen M Robbins, Donna L Senger
PURPOSE: Glioblastoma is one of the most lethal cancers in humans, and with existing therapy, survival remains at 14.6 months. Current barriers to successful treatment include their infiltrative behavior, extensive tumor heterogeneity, and the presence of a stem-like population of cells, termed brain tumor-initiating cells (BTIC) that confer resistance to conventional therapies. EXPERIMENTAL DESIGN: To develop therapeutic strategies that target BTICs, we focused on a repurposing approach that explored already-marketed (clinically approved) drugs for therapeutic potential against patient-derived BTICs that encompass the genetic and phenotypic heterogeneity of glioblastoma observed clinically...
August 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/26356671/disulfiram-anti-cancer-efficacy-without-copper-overload-is-enhanced-by-extracellular-h2o2-generation-antagonism-by-tetrathiomolybdate
#15
Ali Calderon-Aparicio, Mary Strasberg-Rieber, Manuel Rieber
HIGHLIGHTS: HASH(0x44b0618) BACKGROUND: Cu/Zn superoxide dismutases (SODs) like the extracellular SOD3 and cytoplasmic SOD1 regulate cell proliferation by generating hydrogen peroxide (H2O2). This pro-oxidant inactivates essential cysteine residues in protein tyrosine phosphatases (PTP) helping receptor tyrosine kinase activation by growth factor signaling, and further promoting downstream MEK/ERK linked cell proliferation. Disulfiram (DSF), currently in clinical cancer trials is activated by copper chelation, being potentially capable of diminishing the copper dependent activation of MEK1/2 and SOD1/SOD3 and promoting reactive oxygen species (ROS) toxicity...
October 6, 2015: Oncotarget
https://www.readbyqxmd.com/read/26254539/copper-improves-the-anti-angiogenic-activity-of-disulfiram-through-the-egfr-src-vegf-pathway-in-gliomas
#16
Yi Li, Shi-Yuan Fu, Li-Hui Wang, Fang-Yang Wang, Nan-Nan Wang, Qi Cao, Ya-Ting Wang, Jing-Yu Yang, Chun-Fu Wu
Disulfiram (DSF) possesses anticancer activity by inducing apoptosis in vitro and in vivo in a copper (Cu)-dependent manner. DSF also potently inhibits angiogenesis, but the effect of Cu on this anti-angiogenic activity is unknown. Here we show that DSF inhibits the proliferation, migration, invasion, adhesion and complex tube formation of human umbilical vascular endothelial cells (HUVECs). Aortic ring assays and Matrigel plug assays revealed that DSF significantly inhibited the formation of microvessels. Importantly, Cu improved the anti-angiogenic activity of DSF in all these assays, while copper alone had no effect...
December 1, 2015: Cancer Letters
https://www.readbyqxmd.com/read/26239994/antileishmanial-activity-of-disulfiram-and-thiuram-disulfide-analogs-in-an-ex-vivo-model-system-is-selectively-enhanced-by-the-addition-of-divalent-metal-ions
#17
Alex G Peniche, Adam R Renslo, Peter C Melby, Bruno L Travi
Current treatments for cutaneous and visceral leishmaniasis are toxic, expensive, difficult to administer, and limited in efficacy and availability. Disulfiram has primarily been used to treat alcoholism. More recently, it has shown some efficacy as therapy against protozoan pathogens and certain cancers, suggesting a wide range of biological activities. We used an ex vivo system to screen several thiuram disulfide compounds for antileishmanial activity. We found five compounds (compound identifier [CID] 7188, 5455, 95876, 12892, and 3117 [disulfiram]) with anti-Leishmania activity at nanomolar concentrations...
October 2015: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/26033731/disulfiram-and-copper-ions-kill-mycobacterium-tuberculosis-in-a-synergistic-manner
#18
Alex G Dalecki, Mehri Haeili, Santosh Shah, Alexander Speer, Michael Niederweis, Olaf Kutsch, Frank Wolschendorf
Tuberculosis is a severe disease affecting millions worldwide. Unfortunately, treatment strategies are hampered both by the prohibitively long treatment regimen and the rise of drug-resistant strains. Significant effort has been expended in the search for new treatments, but few options have successfully emerged, and new treatment modalities are desperately needed. Recently, there has been growing interest in the synergistic antibacterial effects of copper ions (Cu(II/I)) in combination with certain small molecular compounds, and we have previously reported development of a drug screening strategy to harness the intrinsic bactericidal properties of Cu(II/I)...
August 2015: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/25846272/disulfiram-copper-disulfiram-damages-multiple-protein-degradation-and-turnover-pathways-and-cytotoxicity-is-enhanced-by-metformin-in-oesophageal-squamous-cell-carcinoma-cell-lines
#19
Rupal Jivan, Leonard Howard Damelin, Monica Birkhead, Amanda Louise Rousseau, Robin Bruce Veale, Demetra Mavri-Damelin
Disulfiram (DSF), used since the 1950s in the treatment of alcoholism, is reductively activated to diethyldithiocarbamate and both compounds are thiol-reactive and readily complex copper. More recently DSF and copper-DSF (Cu-DSF) have been found to exhibit potent anticancer activity. We have previously shown that the anti-diabetic drug metformin is anti-proliferative and induces an intracellular reducing environment in oesophageal squamous cell carcinoma (OSCC) cell lines. Based on these observations, we investigated the effects of Cu-DSF and DSF, with and without metformin, in this present study...
October 2015: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/25769405/disulfiram-dsf-acts-as-a-copper-ionophore-to-induce-copper-dependent-oxidative-stress-and-mediate-anti-tumor-efficacy-in-inflammatory-breast-cancer
#20
Jennifer L Allensworth, Myron K Evans, François Bertucci, Amy J Aldrich, Richard A Festa, Pascal Finetti, Naoto T Ueno, Rachid Safi, Donald P McDonnell, Dennis J Thiele, Steven Van Laere, Gayathri R Devi
Cancer cells often have increased levels of reactive oxygen species (ROS); however, acquisition of redox adaptive mechanisms allows for evasion of ROS-mediated death. Inflammatory breast cancer (IBC) is a distinct, advanced BC subtype characterized by high rates of residual disease and recurrence despite advances in multimodality treatment. Using a cellular model of IBC, we identified an oxidative stress response (OSR) signature in surviving IBC cells after administration of an acute dose of an ROS inducer...
June 2015: Molecular Oncology
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