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disulfiram copper

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https://www.readbyqxmd.com/read/28709722/involvement-of-dopamine-beta-hydroxylase-in-the-neuroendocrine-immune-regulatory-network-of-white-shrimp-litopenaeus-vannamei
#1
Winton Cheng, Ya-Wen Ka, Chin-Chyuan Chang
In shrimp, the biosynthesis of catecholamines, including dopamine and norepinephrine, is required for physiological and immunological responses against stress. Dopamine beta-hydroxylase (DBH), a copper-containing monooxygenase enzyme that plays an important role in catecholamine synthesis of the neuroendocrine regulatory network, was identified in Litopenaeus vannamei. In the present study, the potential role of DBH in the immunocompetence of L. vannamei was further estimated by depleting DBH by pharmaceutical inhibition of disulfiram and a gene silencing technique of L...
July 11, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28615941/development-and-optimization-of-an-injectable-formulation-of-copper-diethyldithiocarbamate-an-active-anticancer-agent
#2
Mohamed Wehbe, Malathi Anantha, Minghan Shi, Ada Wai-Yin Leung, Wieslawa H Dragowska, Léon Sanche, Marcel B Bally
Copper diethyldithiocarbamate (Cu(DDC)2) is the active anticancer agent generated when disulfiram (DSF) is provided in the presence of copper. To date, research directed toward repurposing DSF as an anticancer drug has focused on administration of DSF and copper in combination, efforts that have proven unsuccessful in clinical trials. This is likely due to the inability to form Cu(DDC)2 at relevant concentrations in regions of tumor growth. Little effort has been directed toward the development of Cu(DDC)2 because of the inherent aqueous insolubility of the complex...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28528648/copper-and-antibiotics-discovery-modes-of-action-and-opportunities-for-medicinal-applications
#3
Alex G Dalecki, Cameron L Crawford, Frank Wolschendorf
Copper is a ubiquitous element in the environment as well as living organisms, with its redox capabilities and complexation potential making it indispensable for many cellular functions. However, these same properties can be highly detrimental to prokaryotes and eukaryotes when not properly controlled, damaging many biomolecules including DNA, lipids, and proteins. To restrict free copper concentrations, all bacteria have developed mechanisms of resistance, sequestering and effluxing labile copper to minimize its deleterious effects...
2017: Advances in Microbial Physiology
https://www.readbyqxmd.com/read/28518151/disulfiram-copper-selectively-eradicates-aml-leukemia-stem-cells-in-vitro-and-in-vivo-by-simultaneous-induction-of-ros-jnk-and-inhibition-of-nf-%C3%AE%C2%BAb-and-nrf2
#4
Bing Xu, Shiyun Wang, Rongwei Li, Kai Chen, Lingli He, Manman Deng, Vinodh Kannappan, Jie Zha, Huijuan Dong, Weiguang Wang
Acute myeloid leukemia (AML) is a heterogeneous malignancy. Despite the advances in past decades, the clinical outcomes of AML patients remain poor. Leukemia stem cells (LSCs) is the major cause of the recurrence of AML even after aggressive treatment making, promoting development of LSC-targeted agents is an urgent clinical need. Although the antitumor activity of disulfiram (DS), an approved anti-alcoholism drug, has been demonstrated in multiple types of tumors including hematological malignancies such as AML, it remains unknown whether this agent would also be able to target cancer stem cells like LSCs...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28460441/inflammatory-breast-cancer-tumor-emboli-express-high-levels-of-anti-apoptotic-proteins-use-of-a-quantitative-high-content-and-high-throughput-3d-ibc-spheroid-assay-to-identify-targeting-strategies
#5
Jay Arora, Scott J Sauer, Michael Tarpley, Peter Vermeulen, Charlotte Rypens, Steven Van Laere, Kevin P Williams, Gayathri R Devi, Mark W Dewhirst
Inflammatory breast cancer (IBC) is one of the most lethal breast cancer variants; with existing therapy, 5-yr survival rate is only 35%. Current barriers to successful treatment of IBC include frequent infiltration and the presence of tumor cell clusters, termed tumor emboli, within the breast parenchyma and lymphatics. Prior studies have identified the role of anti-apoptotic signaling, in particular hyperactivation of NFκB and its target genes, in IBC pathobiology and therapeutic resistance. The objectives of this study were to: (1) determine if IBC tumor emboli express anti-apoptotic proteins and (2) develop a high content, multiparametric assay to assess the morphology of the IBC 3D spheroids and to optimize a high throughput format to screen for compounds that can inhibit the formation of the IBC tumor clusters/embolic structures...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28373070/disulfiram-suppresses-cancer-stem-like-properties-and-stat3-signaling-in-triple-negative-breast-cancer-cells
#6
Yoon-Jae Kim, Ji Young Kim, Nahyun Lee, Eunhye Oh, Daeil Sung, Tae-Min Cho, Jae Hong Seo
In the presence of copper (Cu), disulfiram (DSF) suppresses properties associated with cancer stem cells (CSCs) in breast cancer, but the mechanism of action is poorly understood. In the present study, we observed that DSF/Cu treatment induced apoptosis, mediated by caspase-3 activation in triple-negative breast cancer (TNBC) cells. DSF/Cu treatment also specifically targeted CSC-like cell populations, marked by the inhibition of ALDH1 activity, the suppression of CD44+/CD24-and CD49f+/CD24 + subpopulations, and the subsequent impairment of mammosphere formation...
May 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28344087/subacute-alcohol-and-or-disulfiram-intake-affects-bioelements-and-redox-status-in-rat-testes
#7
Ana Djuric, Aida Begic, Borko Gobeljic, Ana Pantelic, Goran Zebic, Ivana Stevanovic, Dragan Djurdjevic, Milica Ninkovic, Vera Prokic, Ivan Stanojevic, Danilo Vojvodic, Mirjana Djukic
The aim of the study was to investigate if alcohol and disulfiram (DSF) individually and in combination affect bioelements' and red-ox homeostasis in testes of the exposed rats. The animals were divided into groups according to the duration of treatments (21 and/or 42 days): C21/C42 groups (controls); OL21 and OL22-42 groups (0.5 mL olive oil intake); A1-21 groups (3 mL 20% ethanol intake); DSF1-21 groups (178.5 mg DSF/kg/day intake); and A21+DSF22-42 groups (the DSF ingestion followed previous 21 days' treatment with alcohol)...
March 24, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28143565/disulfiram-overcomes-bortezomib-and-cytarabine-resistance-in-down-syndrome-associated-acute-myeloid-leukemia-cells
#8
Ranjan Bista, David W Lee, Oliver B Pepper, David O Azorsa, Robert J Arceci, Eiman Aleem
BACKGROUND: Children with Down syndrome (DS) have increased risk for developing AML (DS-AMKL), and they usually experience severe therapy-related toxicities compared to non DS-AMKL. Refractory/relapsed disease has very poor outcome, and patients would benefit from novel, less toxic, therapeutic strategies that overcome resistance. Relapse/resistance are linked to cancer stem cells with high aldehyde dehydrogenase (ALDH) activity. The purpose of the present work was to study less toxic alternative therapeutic agents for relapsed/refractory DS-AMKL...
February 1, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28102089/disulfiram-moderately-restores-impaired-hepatic-redox-status-of-rats-subchronically-exposed-to-cadmium
#9
Aida Begic, Ana Djuric, Milica Ninkovic, Ivana Stevanovic, Dragan Djurdjevic, Milos Pavlovic, Katarina Jelic, Ana Pantelic, Goran Zebic, Bratislav Dejanovic, Ivan Stanojevic, Danilo Vojvodic, Petar Milosavljevic, Mirjana Djukic, Luciano Saso
Examination of cadmium (Cd) toxicity and disulfiram (DSF) effect on liver was focused on oxidative stress (OS), bioelements status, morphological and functional changes. Male Wistar rats were intraperitoneally treated with 1 mg CdCl2/kg BW/day; orally with 178.5 mg DSF/kg BW/day for 1, 3, 10 and 21 days; and co-exposed from 22nd to 42nd day. The co-exposure nearly restored previously suppressed total superoxide dismutase (SOD), catalase (CAT) and increased glutathione peroxidase (GPx) activities; increased previously reduced glutathione reductase (GR) and total glutathione-S-transferase (GST) activities; reduced previously increased superoxide anion radical (O2(·-)) and malondialdehyde (MDA) levels; increased zinc (Zn) and iron (Fe), and decreased copper (Cu) (yet above control value), while magnesium (Mg) was not affected; and decreased serum alanine aminotransferases (ALT) levels...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/27894956/disulfiram-induces-anoikis-and-suppresses-lung-colonization-in-triple-negative-breast-cancer-via-calpain-activation
#10
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...
February 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27793743/dopamine-beta-hydroxylase-participate-in-the-immunoendocrine-responses-of-hypothermal-stressed-white-shrimp-litopenaeus-vannamei
#11
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
#12
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
#13
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...
September 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27521693/poly-lactic-co-glycolic-acid-controlled-delivery-of-disulfiram-to-target-liver-cancer-stem-like-cells
#14
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, Xiu-Wu 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...
February 2017: 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
#15
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
#16
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...
November 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
#17
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
#18
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
#19
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...
December 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27175597/copper-as-a-target-for-prostate-cancer-therapeutics-copper-ionophore-pharmacology-and-altering-systemic-copper-distribution
#20
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
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