Search Our Scientific Publications & Authors

J Neurooncol 2019 Feb 15. Epub 2019 Feb 15.

Washington University School of Medicine, St. Louis, MO, USA.

Purpose: Preclinical studies have suggested promising activity for the combination of disulfiram and copper (DSF/Cu) against glioblastoma (GBM) including re-sensitization to temozolomide (TMZ). A previous phase I study demonstrated the safety of combining DSF/Cu with adjuvant TMZ for newly diagnosed GBM. This phase II study aimed to estimate the potential effectiveness of DSF/Cu to re-sensitize recurrent GBM to TMZ. Read More

Prostate 2019 Mar 29;79(4):352-362. Epub 2018 Nov 29.

Laboratory of Genome Integrity, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.

Background: Castration-resistant prostate cancer (PCa) represents a serious health challenge. Based on mechanistically-supported rationale we explored new therapeutic options based on clinically available drugs with anticancer effects, including inhibitors of PARP1 enzyme (PARPi), and histone deacetylases (vorinostat), respectively, and disulfiram (DSF, known as alcohol-abuse drug Antabuse) and its copper-chelating metabolite CuET that inhibit protein turnover.

Methods: Drugs and their combination with ionizing radiation (IR) were tested in various cytotoxicity assays in three human PCa cell lines including radio-resistant stem-cell like derived cells. Read More

Toxicon 2019 Jan 12;157:53-65. Epub 2018 Nov 12.

Dept. for Clinical Toxicology at II, Med. Klinik, TU, München, Munich, Germany.

Mushroom poisoning is a significant and increasing form of toxin-induced-disease. Existing classifications of mushroom poisoning do not include more recently described new syndromes of mushroom poisoning and this can impede the diagnostic process. We reviewed the literature on mushroom poisoning, concentrating on the period since the current major classification published in 1994, to identify all new syndromes of poisoning and organise them into a new integrated classification, supported by a new diagnostic algorithm. Read More

Biomed Pharmacother 2018 Mar 20;99:561-569. Epub 2018 Feb 20.

Hematologic Malignancies Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

The majority of acute myeloid leukaemia (AML) patients will die from their disease or therapy-related complications. There is an inevitable need to improve the survival of AML patients. Previous studies show that disulfiram (DSF), an anti-alcoholism drug with a low toxicity profile, demonstrates anticancer behaviors. Read More

Acta Biomater 2018 07 25;75:63-74. Epub 2018 May 25.

Charles Institute of Dermatology, School of Medicine, University College Dublin, Dublin 4, Ireland. Electronic address:

The injectable hydrogel with desirable biocompatibility and tunable properties can improve the efficacy of stem cell-based therapy. However, the development of injectable hydrogel remains a great challenge due to the restriction of crosslinking efficiency, mechanical properties, and potential toxicity. Here, we report that a new injectable hydrogel system was fabricated from hyperbranched multi-acrylated poly(ethylene glycol) macromers (HP-PEGs) and thiolated hyaluronic acid (HA-SH) and used as a stem cell delivery and retention platform. Read More

Bioorg Med Chem Lett 2018 05 10;28(8):1298-1302. Epub 2018 Mar 10.

Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV, USA; Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA. Electronic address:

Sixteen disulfides derived from disulfiram (Antabuse™) were evaluated as antibacterial agents. Derivatives with hydrocarbon chains of seven and eight carbons in length exhibited antibacterial activity against Gram-positive Staphylococcus, Streptococcus, Enterococcus, Bacillus, and Listeria spp. A comparison of the cytotoxicity and microsomal stability with disulfiram further revealed that the eight carbon chain analog was of lower toxicity to human hepatocytes and has a longer metabolic half-life. Read More

Neurology 2018 Mar 9;90(11):518-519. Epub 2018 Feb 9.

From Sir Jamshedjee Jeejeebhoy Hospital, Mumbai, India.

J Neurooncol 2018 May 27;138(1):105-111. Epub 2018 Jan 27.

Department of Neurosurgery, Washington University School of Medicine, St Louis, MO, 63110, USA.

Disulfiram has shown promising activity including proteasome inhibitory properties and synergy with temozolomide in preclinical glioblastoma (GBM) models. In a phase I study for newly diagnosed GBM after chemoradiotherapy, we have previously reported our initial dose-escalation results combining disulfiram with adjuvant temozolomide and established the maximum tolerated dose (MTD) as 500 mg per day. Here we report the final results of the phase I study including an additional dose-expansion cohort of disulfiram with concurrent copper. Read More

Acta Biomater 2018 03 30;68:113-124. Epub 2017 Dec 30.

Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, 715 Sumter St., Columbia, SC 29208, United States. Electronic address:

Disulfiram (DSF), an FDA approved drug for the treatment of alcoholism, degrades to therapeutically active diethyldithiocarbamate (DDTC) in the body by reduction. Hereby, we developed a redox sensitive DDTC-polymer conjugate for targeted cancer therapy. It was found that the DDTC-polymer conjugate modified with a β-d-galactose receptor targeting ligand can self-assemble into LDNP nanoparticle and efficiently enter cancer cells by receptor-mediated endocytosis. Read More

Invest Ophthalmol Vis Sci 2017 12;58(14):6408-6418

Department of ophthalmology, Ludwig-Maximilians-University, Munich, Germany.

Purpose: Numerous pharmacologic substances have been proposed for preventing posterior capsule opacification (PCO). The following trial was to compare those drugs to find more suitable options. IOL should then be modified by the pharmaceuticals as a drug-delivery device. Read More

Oncotarget 2017 Sep 25;8(39):65900-65916. Epub 2017 Jul 25.

Radiation Oncology, Institute of Cancer Sciences, Wolfson Wohl Translational Cancer Research Center, University of Glasgow, Bearsden, Glasgow, UK.

The disulfiram and copper complex (DSF:Cu) has emerged as a potent radiosensitising anti-cancer agent. The ability of copper to stabilise DSF in a planar conformation and to inhibit DNA replication enzymes stimulated our investigation of the effect of DSF:Cu on cell cycle regulation. Flow cytometry and immunoblotting were used to assess the effect of DSF:Cu on cell cycle progression of the neuroblastoma cell line SK-N-BE(2c) and the glioma cell line UVW. Read More

Free Radic Biol Med 2017 12 30;113:143-156. Epub 2017 Sep 30.

State Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Anhui Agricultural University, Hefei, Anhui, China; International Joint Research Laboratory of Tea Chemistry and Health Effects, Anhui Agricultural University, Hefei, Anhui, China. Electronic address:

Dithiocarbamates (DTC) are widely used in agricultural, industrial and therapeutic domains. There are ample opportunities for human exposure to DTC. Green tea extracts, with epigallocatechin-3-gallate (EGCG) being the most abundant constituent, have been used as dietary supplements for body weight reduction. Read More

EMBO Mol Med 2017 10;9(10):1398-1414

Department of Oncology, Genome Stability and Tumorigenesis Group, The CR-UK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK

Maintenance of genome integrity requires the functional interplay between Fanconi anemia (FA) and homologous recombination (HR) repair pathways. Endogenous acetaldehyde, a product of cellular metabolism, is a potent source of DNA damage, particularly toxic to cells and mice lacking the FA protein FANCD2. Here, we investigate whether HR-compromised cells are sensitive to acetaldehyde, similarly to FANCD2-deficient cells. Read More

Recent Pat Anticancer Drug Discov 2017 ;12(3):260-271

Biochemistry Department, Faculty of Science, Alexandria University, Alexandria. Egypt.

Background: Different strategies against colon cancer are accompanied by treatment failure, because of drug toxicity toward normal cells and cancer stem cells (CSCs) resistance. However, previous patent evaluated liposome that encapsulated inhibitor of CSCs' aldehyde dehydrogenase (ALDH)1; disulfiram, for targeting breast CSCs. Liposome has disadvantages due to its hydrophobicity. Read More

Food Chem Toxicol 2017 Jul 24;105:44-51. Epub 2017 Mar 24.

Department for Toxicology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia. Electronic address:

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): C/C groups (controls); OL and OL groups (0.5 mL olive oil intake); A groups (3 mL 20% ethanol intake); DSF groups (178. Read More

Toxicol Lett 2017 Apr 12;272:60-67. Epub 2017 Mar 12.

Industrial Toxicology and Health Effects Research Group, National Institute of Occupational Safety and Health, Japan.

1,2-Dichloropropane (1,2-DCP), a synthetic chlorinated solvent, was recently classified as carcinogenic. Genotoxic events are known as a crucial step in the initiation of cancer. However, studies on the genotoxicity of 1,2-DCP are very limited, particularly studies investigating the mechanism behind DNA damage by 1,2-DCP. Read More

Clin Neurol Neurosurg 2017 03 18;154:109. Epub 2017 Jan 18.

Department of Anesthesiology and Critical Care Medicine, University Hospital of Patras, School of Medicine University of Patras Rion-Patras, Greece. Electronic address:

J Enzyme Inhib Med Chem 2017 Dec;32(1):478-489

h Department of Physiology and Pharmacology, Sapienza University , Rome , Italy.

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 CdCl/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. Read More

Clin Neurol Neurosurg 2017 Jan 10;152:12-15. Epub 2016 Nov 10.

Neurology Department, Centro Hospitalar Vila Nova de Gaia/Espinho, Porto, Portugal.

Disulfiram (tetraethylthiuram disulfide) has been used for the treatment of alcohol dependence. An axonal sensory-motor polyneuropathy with involvement of cranial pairs due to disulfiram is exceedingly rare. The authors report a unique case of an extremely severe axonal polyneuropathy involving cranial nerves that developed within weeks after a regular dosage of 500mg/day disulfiram. Read More

Oncotarget 2016 Jun;7(26):40348-40361

Faculty of Life Sciences, The University of Manchester, Manchester, UK.

Phenotype-guided re-profiling of approved drug molecules presents an accelerated route to developing anticancer therapeutics by bypassing the target-identification bottleneck of target-based approaches and by sampling drugs already in the clinic. Further, combinations incorporating targeted therapies can be screened for both efficacy and toxicity. Previously we have developed an oncogenic-RAS-driven zebrafish melanoma model that we now describe display melanocyte hyperplasia while still embryos. Read More

J Neurosci 2016 08;36(35):9253-66

Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of the Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University, Shanghai 200433, China,

Unlabelled: T-helper 17 (Th17) cells play an important role in the pathogenesis of multiple sclerosis (MS), an autoimmune demyelinating disease that affects the CNS. In the present study, MicroRNA sequencing (miRNA-seq) was performed in mouse Th0 and Th17 cells to determine the critical miRNAs that are related to Th17 differentiation. We found that miR-30a was significantly downregulated during mouse Th17 differentiation. Read More

Pharmacology 2016 27;98(5-6):267-271. Epub 2016 Aug 27.

Department of Pharmacology, Medical School, University of Ioannina, Ioannina, Greece.

Background/aims: Isoniazid (ISO) has been reported to inhibit the hepatic aldehyde dehydrogenase (ALDH) and to cause a disulfiram (DIS)-like reaction, albeit there are no reports demonstrating increased blood acetaldehyde levels after co-administration of ISO with alcohol. The aim of our study was to clarify whether the alcohol intolerance produced by ISO is indeed due to a typical DIS-like reaction.

Methods: DIS and ISO were administered to Wistar rats and the hepatic ethanol (ETH) metabolizing enzyme activities along with the levels of brain monoamines were determined. Read More

Alcohol 2016 08 29;54:51-9. Epub 2016 Jun 29.

Department of Clinical Pharmacology, Medical University Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria.

Human diamine oxidase (hDAO, EC 1.4.3. Read More

Oncotarget 2016 Dec;7(50):82200-82212

Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen, China.

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. Read More

J Trace Elem Med Biol 2016 Dec 9;38:74-80. Epub 2016 Apr 9.

Innlandet Hospital Trust and Hedmark University College, Elverum, Norway, Norway.

Most acute and chronic human metal poisonings are due to oral or inhalation exposure. Almost 80% of published animal experiments on chelation in metal poisoning used single or repeated intraperitoneal, intramuscular or intravenous administration of metal and chelator, impeding extrapolation to clinical settings. Intramuscular administration of dimercaptopropanol (BAL) has until now been used in acute arsenic, lead, and mercury poisonings, but repeated BAL administration increased the brain uptake of As, Pb and Hg in experimental animals. Read More

J Nanobiotechnology 2016 Apr 21;14:32. Epub 2016 Apr 21.

Hematology, Oncology and Stem cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Science, Tehran, Iran.

Background: A folate-receptor-targeted poly (lactide-co-Glycolide) (PLGA)-Polyethylene glycol (PEG) nanoparticle is developed for encapsulation and delivery of disulfiram into breast cancer cells. After a comprehensive characterization of nanoparticles, cell cytotoxicity, apoptosis induction, cellular uptake and intracellular level of reactive oxygen species are analyzed. In vivo acute and chronic toxicity of nanoparticles and their efficacy on inhibition of breast cancer tumor growth is studied. Read More

Mater Sci Eng C Mater Biol Appl 2016 Jun 9;63:587-95. Epub 2016 Mar 9.

Tissue engineering and biomaterials Research Center, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran 14965/161, Iran. Electronic address:

The strong anticancer activity of disulfiram is hindered by its rapid degradation in blood system. A novel folate-receptor-targeted poly (lactide-co-glycolide) (PLGA)-polyethylene glycol (PEG) nanoparticle (NP) is developed for encapsulation and delivery of disulfiram into breast cancer tumor using passive (EPR effect) and active (folate receptor) targeting. The anticancer activity of disulfiram and its effect on caspase-3 activity and cell cycle are studied. Read More

J Control Release 2016 06 27;231:94-102. Epub 2016 Feb 27.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China. Electronic address:

A poly(l-glutamic acid) graft polyethylene glycol-cisplatin complex (PGA-CisPt) performs well in reducing the toxicity of free cisplatin and greatly enhances the accumulation and retention of cisplatin in solid tumors. However, there is a lack of effective treatment options for cisplatin-resistant tumors. A major reason for this is the dense PEG shell, which ensures that the PGA-CisPt maintains a long retention time in the blood that may result in it bypassing the tumor cells or failing to be endocytosed within the tumor microenvironment. Read More

Toxicol Rep 2016 18;3:252-261. Epub 2016 Jan 18.

Janssen Research and Development, LLC, Raritan, NJ 08869, USA.

As legacy toxicogenomics databases have become available, improved data mining approaches are now key to extracting and visualizing subtle relationships between toxicants and gene expression. In the present study, a novel "aggregating bundles of clusters" (ABC) procedure was applied to separate cholestatic from non-cholestatic drugs and model toxicants in the Johnson & Johnson (Janssen) rat liver toxicogenomics database [3]. Drug-induced cholestasis is an important issue, particularly when a new compound enters the market with this liability, with standard preclinical models often mispredicting this toxicity. Read More

J Neurovirol 2016 08 4;22(4):455-63. Epub 2016 Jan 4.

Centre for Biomedical Research, Burnet Institute, 85 Commercial Rd, Melbourne, 3004, VIC, Australia.

Despite the success of combination antiretroviral therapy (cART), HIV persists in long lived latently infected cells in the blood and tissue, and treatment is required lifelong. Recent clinical studies have trialed latency-reversing agents (LRA) as a method to eliminate latently infected cells; however, the effects of LRA on the central nervous system (CNS), a well-known site of virus persistence on cART, are unknown. In this study, we evaluated the toxicity and potency of a panel of commonly used and well-known LRA (panobinostat, romidepsin, vorinostat, chaetocin, disulfiram, hexamethylene bisacetamide [HMBA], and JQ-1) in primary fetal astrocytes (PFA) as well as monocyte-derived macrophages as a cellular model for brain perivascular macrophages. Read More

Aust Prescr 2015 Apr 1;38(2):41-3. Epub 2015 Apr 1.

Lyell McEwin Hospital, Adelaide.

Drug therapy for alcohol dependence should only be used in conjunction with a comprehensive treatment plan. Naltrexone and acamprosate have well established efficacy and are first-line treatments. Naltrexone is recommended for patients aiming to cut down their alcohol intake who do not have severe liver disease or an ongoing need for opioids. Read More

Clin Toxicol (Phila) 2016 1;54(1):56-60. Epub 2015 Dec 1.

a Department of Emergency Medicine , Ghent University Hospital , Ghent , Belgium.

Context: Cyanide poisoning may be caused by acetonitrile, a common industrial organic solvent and laboratory agent.

Objective: To describe the potential use of disulfiram in treating acetonitrile poisoning in a human clinical case and to further study its effect in human liver microsomes in vitro.

Case Details: A 30-year-old man initially presented with a cholinergic toxic syndrome following ingestion of aldicarb. Read More

Indian J Psychiatry 2015 Jul-Sep;57(3):309-10

Department of Psychiatry, Basaveswara Medical College, Hospital & Research Centre, Chitradurga, Karnataka - 577502, India.

Disulfiram is the aversive therapeutic agent which has been used to treat alcohol dependence more than 50 years. It causes the complications like neurological toxicity, postural hypotension, circulatory collapse, mental confusion, etc. The aim of our study was to report a rare case of disulfiram-induced seizures in a patient of alcohol dependence syndrome. Read More

Mol Carcinog 2016 Nov 24;55(11):1843-1857. Epub 2015 Nov 24.

Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, India.

Estrogen Receptor-β (ER-β), a tumor-suppressor in prostate cancer, is epigenetically repressed by hypermethylation of its promoter. DNA-methyltransferases (DNMTs), which catalyze the transfer of methyl-groups to CpG islands of gene promoters, are overactive in cancers and can be inhibited by DNMT-inhibitors to re-express the tumor suppressors. The FDA-approved nucleoside DNMT-inhibitors like 5-Azacytidine and 5-Aza-deoxycytidine carry notable concerns due to their off-target toxicity, therefore non-nucleoside DNMT inhibitors are desirable for prolonged epigenetic therapy. Read More

Cell Signal 2016 Feb 11;28(2):1-6. Epub 2015 Nov 11.

Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, USA; Department of Physiology, Wayne State University, Detroit, MI 48202, USA. Electronic address:

Reactive oxygen species (ROS)-mediated reactive aldehydes induce cellular stress. In cardiovascular diseases such as ischemia-reperfusion injury, lipid-peroxidation derived reactive aldehydes such as 4-hydroxy-2-nonenal (4HNE) are known to contribute to the pathogenesis. 4HNE is involved in ROS formation, abnormal calcium handling and more importantly defective mitochondrial respiration. Read More

Oncotarget 2015 Oct;6(30):29771-81

IVIC, Laboratorio de Bioquimica Celular, CMBC, Altos de Pipe, Caracas, Venezuela.

Highlights:

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. Read More

Mol Oncol 2015 Jun 21;9(6):1155-68. Epub 2015 Feb 21.

Department of Surgery, Duke University Medical Center, Durham, NC, USA; Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA; Department of Pathology, Duke University Medical Center, Durham, NC, USA. Electronic address:

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. Read More

Biochem Pharmacol 2015 Feb 31;93(3):332-42. Epub 2014 Dec 31.

Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, Cardiff, Wales CF10 3NB, UK. Electronic address:

Disulfiram, a clinically used alcohol-deterrent has gained prominence as a potential anti-cancer agent due to its impact on copper-dependent processes. Few studies have investigated zinc effects on disulfiram action, despite it having high affinity for this metal. Here we studied the cytotoxic effects of disulfiram in breast cancer cells, and its relationship with both intra and extracellular zinc. Read More

J Clin Neurophysiol 2014 Dec;31(6):e18-20

Departments of *Neurology and †Family Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, U.S.A.

Disulfiram toxicity can cause multiple neurologic problems, including a reversible distal sensorimotor axonal polyneuropathy. Although electrodiagnosis and biopsy results have been described in the diagnosis and management of patients with disulfiram associated polyneuropathy, neuromuscular ultrasound findings have not been reported. The authors present a case of electrodiagnostically confirmed axonal polyneuropathy with relative sural sparing secondary to disulfiram and describe the neuromuscular ultrasound findings in this individual. Read More

Toxicon 2015 Jan 8;93:68-78. Epub 2014 Nov 8.

Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore, Karnataka, India. Electronic address:

Viperbites undeniably cause local manifestations such as hemorrhage and myotoxicity involving substantial degradation of extracellular matrix (ECM) at the site of envenomation and lead to progressive tissue damage and necrosis. The principle toxin responsible is attributed to snake venom metalloproteases (SVMPs). Treatment of such progressive tissue damage induced by SVMPs has become a challenging task for researchers and medical practitioners who are in quest of SVMPs inhibitors. Read More

Expert Opin Drug Metab Toxicol 2015 Jan 13;11(1):81-94. Epub 2014 Nov 13.

Paris Diderot University, Life Sciences , Paris , France.

Introduction: Thiocarbamates are chemicals widely used as pesticides. Occupational exposure is associated with acute intoxication. Populations can be exposed through food and water. Read More

Oncotarget 2014 Sep;5(17):7471-85

Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, UK.

Breast cancer stem cells (BCSCs) are pan-resistant to different anticancer agents and responsible for cancer relapse. Disulfiram (DS), an antialcoholism drug, targets CSCs and reverses pan-chemoresistance. The anticancer application of DS is limited by its very short half-life in the bloodstream. Read More

Zhonghua Xue Ye Xue Za Zhi 2014 Sep;35(9):848-50

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

Toxicol Sci 2014 May 4;139(1):257-70. Epub 2014 Feb 4.

Division of Endocrinology and Center for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, Lucknow 226021, India.

Dithiocarbamates (DTC), a sulfhydryl group containing compounds, are extensively used by humans that include metam and thiram due to their pesticide properties, and disulfiram (DSF) as an alcohol deterrent. We screened these DTC in an osteoblast viability assay. DSF exhibited the highest cytotoxicity (IC50 488nM). Read More

Neurol India 2013 Sep-Oct;61(5):539-40

Department of Neurology, Post Graduate Institute of Medical Education and Research and Dr. Ram Manohar Lohia Hospital, New Delhi, India.

Chudoku Kenkyu 2013 Sep;26(3):223-5

Cancer Chemother Pharmacol 2013 Dec 24;72(6):1195-204. Epub 2013 Sep 24.

Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, 15213, USA.

Purpose: Benzaldehyde dimethane sulfonate (DMS612, NSC281612, BEN) is an alkylator with activity against renal cell carcinoma, currently in phase I trials. In blood, BEN is rapidly metabolized into its highly reactive carboxylic acid (BA), presumably the predominant alkylating species. We hypothesized that BEN is metabolized to BA by aldehyde dehydrogenase (ALDH) and aimed to increase BEN exposure in blood and tissues by inhibiting ALDH with disulfiram, thereby shifting BA production from blood to tissues. Read More

Chemotherapy 2013 14;59(2):112-20. Epub 2013 Sep 14.

Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.

Background: Resistance of cancer cells to chemotherapeutic agents is a major cause of treatment failure in patients with cancer. The drug resistance of tumor cells can be significantly modified by specific features of tumor microenvironment, such as oxygen depletion (hypoxia), glucose/energy deprivation and acidosis.

Methods: The effects of acidic tumor-like microenvironment on cytotoxicity of antabuse (disulfiram, DSF)/Cu(2+) complexes to MCF-7 breast carcinoma and HT-29 colon carcinoma cells were studied. Read More

Eur Respir J 2014 Mar 29;43(3):884-97. Epub 2013 Aug 29.

University Medical Center Groningen, Dept of Hospital and Clinical Pharmacy, Groningen.

Treatment of multidrug-resistant (MDR) tuberculosis (TB) is challenging because of the high toxicity of second-line drugs and the longer treatment duration than for drug-susceptible TB patients. In order to speed up novel treatment for MDR-TB, we suggest considering expanding the indications of already available drugs. Six drugs with antimicrobial activity (phenothiazine, metronidazole, doxycycline, disulfiram, tigecycline and co-trimoxazole) are not listed in the World Health Organization guidelines on MDR-TB treatment but could be potential candidates for evaluation against Mycobacterium tuberculosis. Read More

Cell Cycle 2013 Sep 12;12(18):3013-24. Epub 2013 Aug 12.

Department of Laboratory Medicine and Pathobiology; University of Toronto; Toronto, Ontario, Canada.

Triple-negative breast cancer (TNBC) represents an aggressive subtype, for which radiation and chemotherapy are the only options. Here we describe the identification of disulfiram, an FDA-approved drug used to treat alcoholism, as well as the related compound thiram, as the most potent growth inhibitors following high-throughput screens of 3185 compounds against multiple TNBC cell lines. The average IC50 for disulfiram was ~300 nM. Read More