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  1 / 19 MEDLINE  
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[PMID]:28887129
[Au] Autor:Hasinoff BB; Patel D
[Ad] Endereço:College of Pharmacy, Apotex Centre, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada. Electronic address: B_Hasinoff@UManitoba.ca.
[Ti] Título:Disulfiram is a slow-binding partial noncompetitive inhibitor of 20S proteasome activity.
[So] Source:Arch Biochem Biophys;633:23-28, 2017 Nov 01.
[Is] ISSN:1096-0384
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The alcohol abuse drug disulfiram has also been shown to exhibit potent cell growth inhibitory and anticancer activity. While a number of cellular and animal studies have suggested that disulfiram exhibits its anticancer activity through interaction with the proteasome, direct evidence for inhibition of proteasome activity is lacking. In this study we show that disulfiram potently inhibits the chymotrypsin-like activity of purified human 20S proteasome at low micromolar pharmacological concentrations. The enzyme progress curves displayed characteristics of a slow-binding reaction, similar to that observed for the FDA-approved proteasomal-targeted anticancer drugs bortezomib and carfilzomib. The apparent second order rate constant for reaction with 20s proteasome that was derived from an analysis of the progress curves was about 250-fold smaller than for bortezomib and carfilzomib. The concentration dependence of the enzyme kinetics was consistent with partial noncompetitive inhibition, whereby the putative disulfiram-proteasome adduct retains, partial but decreased enzyme activity. Disulfiram, which is known to have a high affinity for protein thiols, likely reacted with a non-critical cysteine residue, and not at the proteasome substrate binding site.
[Mh] Termos MeSH primário: Inibidores de Acetaldeído Desidrogenases/farmacologia
Dissulfiram/farmacologia
Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos
Inibidores de Proteassoma/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/farmacologia
Bortezomib/farmacologia
Sistema Livre de Células/efeitos dos fármacos
Sistema Livre de Células/enzimologia
Seres Humanos
Cinética
Oligopeptídeos/farmacologia
Complexo de Endopeptidases do Proteassoma/metabolismo
Ligação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetaldehyde Dehydrogenase Inhibitors); 0 (Antineoplastic Agents); 0 (Oligopeptides); 0 (Proteasome Inhibitors); 69G8BD63PP (Bortezomib); 72X6E3J5AR (carfilzomib); EC 3.4.25.1 (Proteasome Endopeptidase Complex); TR3MLJ1UAI (Disulfiram)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170910
[St] Status:MEDLINE


  2 / 19 MEDLINE  
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[PMID]:28864067
[Au] Autor:Cong J; Wang Y; Zhang X; Zhang N; Liu L; Soukup K; Michelakos T; Hong T; DeLeo A; Cai L; Sabbatino F; Ferrone S; Lee H; Levina V; Fuchs B; Tanabe K; Lillemoe K; Ferrone C; Wang X
[Ad] Endereço:Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
[Ti] Título:A novel chemoradiation targeting stem and nonstem pancreatic cancer cells by repurposing disulfiram.
[So] Source:Cancer Lett;409:9-19, 2017 Nov 28.
[Is] ISSN:1872-7980
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Pancreatic ductal adenocarcinoma (PDAC) has a 5-year relative survival rate of 8% and is projected to be the second leading cause of cancer death by 2030, underscoring the urgency to develop new strategies to improve current therapeutic modalities for PDAC. Targeting pancreatic cancer stem cells (PCSCs), which are resistant to radiation and chemotherapy, is a promising strategy. A novel approach which can be readily clinically translated is to repurpose disulfiram (DSF), a drug for treating alcoholism, to target PCSCs. Chemoradiation or the combination of chemotherapy agents FOLFIRINOX, currently standard care for PDAC, can increase stemness in some established or primary PDAC cell lines. However, DSF in the presence of exogenously or endogenously supplied copper (Cu), when combined with chemotherapy or chemoradiation, targets both PCSCs and nonstem PDAC cells. Previously, we demonstrated that DSF/Cu effectively targets breast cancer stem cells in the context of fractionated radiation (FIR) by inhibiting the NF-κB-stemness gene pathway. Therefore, the hypothesis that PCSCs can be effectively targeted by incorporating DSF/Cu into the standard chemoradiation regimen consisting of 5-FU and FIR was investigated and found to be effective in vitro in targeting PCSCs, identified as either ALDH or CD24+/CD44+/ESA+ or sphere-forming cells, as well as nonstem PDAC cells. In vivo, the combination of IR+5-FU+DSF/Cu was more effective (72.46%) than either IR+5-FU (30.32%) or IR+FOLFIRINOX therapy (43.04%) in inhibiting growth of the mouse Panc02 tumor. These encouraging results provide a solid foundation for clinical trials to improve the outcomes of the current standard chemoradiation therapy regimen for PDAC.
[Mh] Termos MeSH primário: Carcinoma Ductal Pancreático/tratamento farmacológico
Carcinoma Ductal Pancreático/radioterapia
Dissulfiram/farmacologia
Células-Tronco Neoplásicas/efeitos dos fármacos
Células-Tronco Neoplásicas/efeitos da radiação
Neoplasias Pancreáticas/tratamento farmacológico
Neoplasias Pancreáticas/radioterapia
[Mh] Termos MeSH secundário: Inibidores de Acetaldeído Desidrogenases/farmacologia
Animais
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Carcinoma Ductal Pancreático/genética
Carcinoma Ductal Pancreático/patologia
Linhagem Celular Tumoral
Quimiorradioterapia
Cobre/farmacologia
Reposicionamento de Medicamentos
Feminino
Fluoruracila/farmacologia
Seres Humanos
Camundongos
Camundongos Endogâmicos C57BL
Células-Tronco Neoplásicas/patologia
Neoplasias Pancreáticas/genética
Neoplasias Pancreáticas/patologia
Radiossensibilizantes/farmacologia
Distribuição Aleatória
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetaldehyde Dehydrogenase Inhibitors); 0 (Radiation-Sensitizing Agents); 789U1901C5 (Copper); C955P95064 (cuprous chloride); TR3MLJ1UAI (Disulfiram); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170903
[St] Status:MEDLINE


  3 / 19 MEDLINE  
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[PMID]:27521693
[Au] Autor:Wang Z; Tan J; McConville C; Kannappan V; Tawari PE; Brown J; Ding J; Armesilla AL; Irache JM; Mei QB; Tan Y; Liu Y; Jiang W; Bian XW; Wang W
[Ad] Endereço:Faculty of Science & Engineering, University of Wolverhampton, Wolverhampton, UK.
[Ti] Título:Poly lactic-co-glycolic acid controlled delivery of disulfiram to target liver cancer stem-like cells.
[So] Source:Nanomedicine;13(2):641-657, 2017 Feb.
[Is] ISSN:1549-9642
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo: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. In combination with copper, DS-PLGA significantly inhibited the liver cancer stem cell population. CI-isobologram showed a remarkable synergistic cytotoxicity between DS-PLGA and 5-FU or sorafenib. It also demonstrated very promising anticancer efficacy and antimetastatic effect in liver cancer mouse model. Both DS and PLGA are FDA approved products for clinical application. Our study may lead to repositioning of DS into liver cancer treatment.
[Mh] Termos MeSH primário: Inibidores de Acetaldeído Desidrogenases/administração & dosagem
Dissulfiram/administração & dosagem
Neoplasias Hepáticas/tratamento farmacológico
Nanopartículas
[Mh] Termos MeSH secundário: Animais
Portadores de Fármacos
Glicóis
Seres Humanos
Ácido Láctico
Ácido Poliglicólico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetaldehyde Dehydrogenase Inhibitors); 0 (Drug Carriers); 0 (Glycols); 26009-03-0 (Polyglycolic Acid); 33X04XA5AT (Lactic Acid); TR3MLJ1UAI (Disulfiram)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160814
[St] Status:MEDLINE


  4 / 19 MEDLINE  
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[PMID]:27882330
[Au] Autor:Pan G; Deshpande M; Thandavarayan RA; Palaniyandi SS
[Ad] Endereço:Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, USA.
[Ti] Título:ALDH2 Inhibition Potentiates High Glucose Stress-Induced Injury in Cultured Cardiomyocytes.
[So] Source:J Diabetes Res;2016:1390861, 2016.
[Is] ISSN:2314-6753
[Cp] País de publicação:Egypt
[La] Idioma:eng
[Ab] Resumo:Aldehyde dehydrogenase (ALDH) gene superfamily consists of 19 isozymes. They are present in various organs and involved in metabolizing aldehydes that are biologically generated. For instance, ALDH2, a cardiac mitochondrial ALDH isozyme, is known to detoxify 4-hydroxy-2-nonenal, a reactive aldehyde produced upon lipid peroxidation in diabetic conditions. We hypothesized that inhibition of ALDH leads to the accumulation of unmetabolized 4HNE and consequently exacerbates injury in cells subjected to high glucose stress. H9C2 cardiomyocyte cell lines were pretreated with 10 M disulfiram (DSF), an inhibitor of ALDH2 or vehicle (DMSO) for 2 hours, and then subjected to high glucose stress {33 mM D-glucose (HG) or 33 mM D-mannitol as an osmotic control (Ctrl)} for 24 hrs. The decrease in ALDH2 activity with DSF pretreatment was higher in HG group when compared to Ctrl group. Increased 4HNE adduct formation with DSF pretreatment was higher in HG group compared to Ctrl group. Pretreatment with DSF leads to potentiated HG-induced cell death in cultured H9C2 cardiomyocytes by lowering mitochondrial membrane potential. Our results indicate that ALDH2 activity is important in preventing high glucose induced cellular dysfunction.
[Mh] Termos MeSH primário: Inibidores de Acetaldeído Desidrogenases/farmacologia
Aldeído-Desidrogenase Mitocondrial/antagonistas & inibidores
Dissulfiram/farmacologia
Glucose/farmacologia
Miócitos Cardíacos/metabolismo
Pressão Osmótica/efeitos dos fármacos
[Mh] Termos MeSH secundário: Linhagem Celular
Seres Humanos
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Miócitos Cardíacos/citologia
Miócitos Cardíacos/efeitos dos fármacos
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetaldehyde Dehydrogenase Inhibitors); 0 (Reactive Oxygen Species); EC 1.2.1.3 (Aldehyde Dehydrogenase, Mitochondrial); IY9XDZ35W2 (Glucose); TR3MLJ1UAI (Disulfiram)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170531
[Lr] Data última revisão:
170531
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161125
[St] Status:MEDLINE


  5 / 19 MEDLINE  
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[PMID]:27831632
[Au] Autor:Celik O; Ersahin A; Acet M; Celik N; Baykus Y; Deniz R; Ozerol E; Ozerol I
[Ad] Endereço:Private Clinic Obstetrics and Gynecology, Usak, Turkey. celiksudenaz@gmail.com.
[Ti] Título:Disulfiram, as a candidate NF-κB and proteasome inhibitor, prevents endometriotic implant growing in a rat model of endometriosis.
[So] Source:Eur Rev Med Pharmacol Sci;20(20):4380-4389, 2016 Oct.
[Is] ISSN:2284-0729
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Disulfiram (DSF) exerts its therapeutic effects through oxidative, proteasome, and nuclear factor kappa beta (NF-κB) pathways. The study was planned to test the impact of DSF on growing of endometriotic implants in rats with experimentally induced endometriosis. PATIENTS AND METHODS: Thirty rats were labeled as the control (n = 8), sham (n = 6), GnRH-agonist (n = 8) and the DSF (n = 8) groups. The rats in the group 3 exposed to single dose leuprolide acetate. The rats in group 4 were treated with DSF for 21 days. The serum activity of oxidant and antioxidant markers, total oxidant status (TOS), total antioxidant status (TAS), interleukin-1ß, and tumor necrosis factor-α (TNF-α) were determined. Implants were processed for NF-κB, PCNA, and CD34 immunostaining. RESULTS: The serum concentration of malondialdehyde in the DSF group was significantly higher than those in other groups. The concentration of TAS, TNF-α, and interleukin-1ß in the DSF group considerably decreased compared to control group. Following treatment with DSF while the percentage of Grade 1 and 2 implants increased the percentage of Grade 3 and 4 implants decreased. The implants disappeared totally in two cases in the DSF group and one case in the GnRH-agonist group. The mean H-Scores of implant NF-κB and PCNA in DSF treated animals were found to significantly lower than those of the control group. CONCLUSIONS: By decreasing NF-κB expression, angiogenesis, and cell proliferation DSF prevents the growth of endometriotic implants.
[Mh] Termos MeSH primário: Inibidores de Acetaldeído Desidrogenases/uso terapêutico
Dissulfiram/uso terapêutico
Endometriose/prevenção & controle
Inibidores de Proteassoma
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Feminino
Seres Humanos
NF-kappa B/metabolismo
Ratos
Fator de Necrose Tumoral alfa
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetaldehyde Dehydrogenase Inhibitors); 0 (NF-kappa B); 0 (Proteasome Inhibitors); 0 (Tumor Necrosis Factor-alpha); TR3MLJ1UAI (Disulfiram)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170804
[Lr] Data última revisão:
170804
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161111
[St] Status:MEDLINE


  6 / 19 MEDLINE  
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[PMID]:27466724
[Au] Autor:Spiegel DR; McCroskey A; Puaa K; Meeker G; Hartman L; Hudson J; Hung YC
[Ad] Endereço:Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, Norfolk, VA.
[Ti] Título:A Case of Disulfiram-Induced Psychosis in a Previously Asymptomatic Patient Maintained on Mixed Amphetamine Salts: A Review of the Literature and Possible Pathophysiological Explanations.
[So] Source:Clin Neuropharmacol;39(5):272-5, 2016 Sep-Oct.
[Is] ISSN:1537-162X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Although perhaps better known as an irreversible aldehyde dehydrogenase inhibitor causing increased acetaldehyde levels after concomitant intake of ethanol, disulfiram or one of its metabolites (diethyldithiocarbamate) also inhibit dopamine ß-hydroxylase, an enzyme that converts dopamine to norepinephrine. This mechanism has been advanced as a possible explanation for the development of psychosis, during disulfiram treatment, either in monotherapy or in combination therapy, when interaction-emergent psychosis could be causal. We present a young woman who was taking mixed amphetamine salts for treatment of attention-deficit/hyperactivity disorder and developed a short-lived psychosis after introduction of disulfiram. The psychotic symptoms resolved after discontinuation of both medications, without the use of antipsychotic drugs. We proceed with a review of the literature of disulfiram-induced psychosis and discuss pathophysiological theories that possibly were involved in our patient's phenomenology.
[Mh] Termos MeSH primário: Inibidores de Acetaldeído Desidrogenases/efeitos adversos
Dissulfiram/efeitos adversos
Psicoses Induzidas por Substâncias/etiologia
[Mh] Termos MeSH secundário: Adulto
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico
Feminino
Seres Humanos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Acetaldehyde Dehydrogenase Inhibitors); TR3MLJ1UAI (Disulfiram)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170120
[Lr] Data última revisão:
170120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160729
[St] Status:MEDLINE
[do] DOI:10.1097/WNF.0000000000000166


  7 / 19 MEDLINE  
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[PMID]:27326831
[Au] Autor:Pyakurel P; Privman Champaloux E; Venton BJ
[Ad] Endereço:Department of Chemistry, University of Virginia , PO Box 400319, Charlottesville, Virginia 22904, United States.
[Ti] Título:Fast-Scan Cyclic Voltammetry (FSCV) Detection of Endogenous Octopamine in Drosophila melanogaster Ventral Nerve Cord.
[So] Source:ACS Chem Neurosci;7(8):1112-9, 2016 Aug 17.
[Is] ISSN:1948-7193
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Octopamine is an endogenous biogenic amine neurotransmitter, neurohormone, and neuromodulator in invertebrates and has functional analogy with norepinephrine in vertebrates. Fast-scan cyclic voltammetry (FSCV) can detect rapid changes in neurotransmitters, but FSCV has not been optimized for octopamine detection in situ. The goal of this study was to characterize octopamine release in the ventral nerve cord of Drosophila larvae for the first time. A FSCV waveform was optimized so that the potential for octopamine oxidation would not be near the switching potential where interferences can occur. Endogenous octopamine release was stimulated by genetically inserting either the ATP sensitive channel, P2X2, or the red-light sensitive channelrhodopsin, CsChrimson, into cells expressing tyrosine decarboxylase (TDC), an octopamine synthesis enzyme. To ensure that release is due to octopamine and not the precursor tyramine, the octopamine synthesis inhibitor disulfiram was applied, and the signal decreased by 80%. Stimulated release was vesicular, and a 2 s continuous light stimulation of CsChrimson evoked 0.22 ± 0.03 µM of octopamine release in the larval ventral nerve cord. Repeated stimulations were stable with 2 or 5 min interstimulation times. With pulsed stimulations, the release was dependent on the frequency of applied light pulse. An octopamine transporter has not been identified, and blockers of the dopamine transporter and serotonin transporter had no significant effect on the clearance time of octopamine, suggesting that they do not take up octopamine. This study shows that octopamine can be monitored in Drosophila, facilitating future studies of how octopamine release functions in the insect brain.
[Mh] Termos MeSH primário: Sistema Nervoso Central/metabolismo
Drosophila melanogaster/metabolismo
Técnicas Eletroquímicas
Regulação da Expressão Gênica/genética
Octopamina/metabolismo
[Mh] Termos MeSH secundário: Inibidores de Acetaldeído Desidrogenases/farmacologia
Inibidores da Captação Adrenérgica/farmacologia
Animais
Animais Geneticamente Modificados
Sistema Nervoso Central/citologia
Sistema Nervoso Central/efeitos dos fármacos
Dissulfiram/farmacologia
Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo
Proteínas de Drosophila/genética
Proteínas de Drosophila/metabolismo
Fluoxetina/análogos & derivados
Fluoxetina/farmacologia
Regulação da Expressão Gênica/efeitos dos fármacos
Luz
Neurônios/metabolismo
Receptores Purinérgicos P2X2/genética
Receptores Purinérgicos P2X2/metabolismo
Reserpina/farmacologia
Rodopsina/genética
Rodopsina/metabolismo
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
Tirosina Descarboxilase/genética
Tirosina Descarboxilase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetaldehyde Dehydrogenase Inhibitors); 0 (Adrenergic Uptake Inhibitors); 0 (Dopamine Plasma Membrane Transport Proteins); 0 (Drosophila Proteins); 0 (GAL4 protein, Drosophila); 0 (Receptors, Purinergic P2X2); 0 (Transcription Factors); 01K63SUP8D (Fluoxetine); 14O50WS8JD (Octopamine); 17NV064B2D (nisoxetine); 8B1QWR724A (Reserpine); 9009-81-8 (Rhodopsin); EC 4.1.1.25 (Tyrosine Decarboxylase); TR3MLJ1UAI (Disulfiram)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160622
[St] Status:MEDLINE
[do] DOI:10.1021/acschemneuro.6b00070


  8 / 19 MEDLINE  
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[PMID]:27238567
[Au] Autor:Kim JY; Cho Y; Oh E; Lee N; An H; Sung D; Cho TM; Seo JH
[Ad] Endereço:Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea.
[Ti] Título:Disulfiram targets cancer stem-like properties and the HER2/Akt signaling pathway in HER2-positive breast cancer.
[So] Source:Cancer Lett;379(1):39-48, 2016 08 28.
[Is] ISSN:1872-7980
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo: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. DSF/Cu treatment induced apoptosis, associated with a marked decrease in HER2, truncated p95HER2, phospho-HER2, HER3, phospho-HER3 and phospho-Akt levels, and p27 nuclear accumulation. This was accompanied by the eradication of cancer stem-like populations, concomitant with the suppression of aldehyde dehydrogenase 1 (ALDH1) activity and mammosphere formation. DSF administration resulted in a significant reduction in tumor growth and an enhancement of apoptosis, as well as HER2 intracellular domain (ICD) and ALDH1A1 downregulation. Our results demonstrate that DSF/Cu induces apoptosis and eliminates cancer stem-like cells via the suppression of HER2/Akt signaling, suggesting that DSF may be potentially effective for the treatment of HER2-positive cancers.
[Mh] Termos MeSH primário: Inibidores de Acetaldeído Desidrogenases/farmacologia
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Apoptose/efeitos dos fármacos
Neoplasias da Mama/tratamento farmacológico
Cobre/farmacologia
Dissulfiram/farmacologia
Células-Tronco Neoplásicas/efeitos dos fármacos
Proteínas Proto-Oncogênicas c-akt/metabolismo
Receptor ErbB-2/metabolismo
[Mh] Termos MeSH secundário: Aldeído Desidrogenase/antagonistas & inibidores
Aldeído Desidrogenase/metabolismo
Animais
Neoplasias da Mama/enzimologia
Neoplasias da Mama/patologia
Inibidor de Quinase Dependente de Ciclina p27/metabolismo
Relação Dose-Resposta a Droga
Feminino
Seres Humanos
Células MCF-7
Camundongos Endogâmicos BALB C
Camundongos Nus
Células-Tronco Neoplásicas/enzimologia
Células-Tronco Neoplásicas/patologia
Fenótipo
Fosforilação
Transdução de Sinais/efeitos dos fármacos
Fatores de Tempo
Carga Tumoral/efeitos dos fármacos
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acetaldehyde Dehydrogenase Inhibitors); 0 (CDKN1B protein, human); 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27); 789U1901C5 (Copper); EC 1.2.1.3 (ALDH1A1 protein, human); EC 1.2.1.3 (Aldehyde Dehydrogenase); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); S2QG84156O (cupric chloride); TR3MLJ1UAI (Disulfiram)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171028
[Lr] Data última revisão:
171028
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160531
[St] Status:MEDLINE


  9 / 19 MEDLINE  
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[PMID]:27013133
[Au] Autor:Hoda M; Pajaniradje S; Shakya G; Mohankumar K; Rajagopalan R
[Ad] Endereço:Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry, India.
[Ti] Título:Anti-proliferative and apoptosis-triggering potential of disulfiram and disulfiram-loaded polysorbate 80-stabilized PLGA nanoparticles on hepatocellular carcinoma Hep3B cell line.
[So] Source:Nanomedicine;12(6):1641-50, 2016 Aug.
[Is] ISSN:1549-9642
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:There is an emerging trend to restudy known drugs for their anti-cancer potential. One such anti-alcoholic drug, disulfiram, with significant anti-cancer potential was studied for its efficacy against Hep3B cell lines, an in vitro model of hepatocellular carcinoma. Simultaneously, we intended to study the effect of polysorbate 80-stabilized PLGA nanoparticles and its DSF-loaded counterpart. Cell and nuclear staining, comet assay, flow cytometry and Western blots were performed. Results suggest that cell proliferation was inhibited by DSF and its PLGA nanoparticles through cell cycle arrest, triggering activation of apoptotic pathways that culminates with cell death. DSF loaded nanoparticles when compared with free DSF, showed significantly lesser effect due to its sustained drug-releasing property, while empty nanoparticles showed negligible influence on Hep3B cells. Our results suggest that DSF alone contributes to cell death, while polysorbate 80-stabilized PLGA nanoparticles show sustained drug release patterns that would potentially lower dosage regimens.
[Mh] Termos MeSH primário: Inibidores de Acetaldeído Desidrogenases/farmacologia
Apoptose/efeitos dos fármacos
Carcinoma Hepatocelular/tratamento farmacológico
Dissulfiram/farmacologia
Neoplasias Hepáticas/tratamento farmacológico
Nanopartículas
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Seres Humanos
Polissorbatos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetaldehyde Dehydrogenase Inhibitors); 0 (Polysorbates); TR3MLJ1UAI (Disulfiram)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160326
[St] Status:MEDLINE


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[PMID]:26711966
[Au] Autor:Song W; Tang Z; Lei T; Wen X; Wang G; Zhang D; Deng M; Tang X; Chen X
[Ad] Endereço:Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, PR China.
[Ti] Título:Stable loading and delivery of disulfiram with mPEG-PLGA/PCL mixed nanoparticles for tumor therapy.
[So] Source:Nanomedicine;12(2):377-86, 2016 Feb.
[Is] ISSN:1549-9642
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: Disulfiram (DSF) showed great potential in an in vitro tumor therapy study; however, those results could not be applied to an in vivo study due to the extreme instability of DSF in blood. Here, we describe a system of methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide)/poly(ε-caprolactone) (mPEG-PLGA/PCL) mixed nanoparticles (NPs) for DSF loading and delivery. By adjusting the mPEG-PLGA/PCL content ratios, the DSF loading capacity increased to 7.8%, while the hydrodynamic radii of the NPs were around 50-100nm. The DSF-loaded NPs showed high stability in distilled water and 10% serum-containing phosphate buffered saline. The NPs efficiently protected DSF from degradation while maintaining its anti-tumor properties. Furthermore, a pharmacokinetics study demonstrated that NP delivery system enhanced the DSF concentration in the blood after tail vein injection. Finally, DSF delivery using this model effectively slowed the growth of a 4T1 murine xenograft tumor. FROM THE CLINICAL EDITOR: The anti-tumor efficacy of the anti-alcoholic drug disulfiram has been known for some time. However, its use in the clinical setting is limited due to the underlying instability of the drug. In this study, the authors utilized a nanocarrier system of mPEG-PLGA/PCL for the delivery of this drug. The promising results may allow encapsulation of other drugs.
[Mh] Termos MeSH primário: Dissuasores de Álcool/uso terapêutico
Neoplasias da Mama/tratamento farmacológico
Dissulfiram/uso terapêutico
Portadores de Fármacos/química
Nanopartículas/química
Poliésteres/química
Polietilenoglicóis/química
[Mh] Termos MeSH secundário: Inibidores de Acetaldeído Desidrogenases/administração & dosagem
Inibidores de Acetaldeído Desidrogenases/sangue
Inibidores de Acetaldeído Desidrogenases/uso terapêutico
Dissuasores de Álcool/administração & dosagem
Dissuasores de Álcool/sangue
Animais
Antineoplásicos/administração & dosagem
Antineoplásicos/sangue
Antineoplásicos/uso terapêutico
Mama/efeitos dos fármacos
Mama/patologia
Neoplasias da Mama/patologia
Dissulfiram/administração & dosagem
Dissulfiram/sangue
Feminino
Seres Humanos
Células MCF-7
Camundongos
Camundongos Endogâmicos BALB C
Nanopartículas/ultraestrutura
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acetaldehyde Dehydrogenase Inhibitors); 0 (Alcohol Deterrents); 0 (Antineoplastic Agents); 0 (Drug Carriers); 0 (Polyesters); 0 (methoxypolyethyleneglycol-poly(lactic-co-glycolic acid)); 24980-41-4 (polycaprolactone); 30IQX730WE (Polyethylene Glycols); TR3MLJ1UAI (Disulfiram)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151230
[St] Status:MEDLINE



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