• Korean Journal of Biological Psychiatry
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• v.3 no.1
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• pp.83-87
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• 1996

The effects of disulfiram implantation therapy have three components : placebo, pharmacological, and psychological effects, However, considering the fact that there is no reported DER(disulfiram-ethanol reaction) in placebo implanted patients and the absorption of implanted disulfiram is not sufficient to produce DER, the major effect of disulfiram implantation is psychological rather than placebo and pharmacological one, Recently, there have been great efforts to develop a new farm of disulfiram which could exert a real pharmacological effect through the heightened bioavailability, To illustrate several examples, there are copolymer consisting of disulfiram and polymer such as polyethylene glycol and PLGA(polyglycolic-co-L-lactic acid) and depot in which disulfiram is dissolved into saline solution containing 5% w/v carboxymethylcellulose or 0.1% polysorbate 80. On the other hand, there has been a continuous research about Me-DTC, an active metabolite of disulfiram, which inhibit ALDH (acetaldehyde dehydrogenase) more potently even at a smaller amount than disulfiram. In the future. In is hoped to develop a new form of disulfiram with high bioavailability at a small amount.

• Journal of Preventive Veterinary Medicine
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• v.42 no.4
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• pp.177-181
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• 2018

Disulfiram is a drug used to treat alcohol dependence. Recent studies have shown that disulfiram also has anti-cancer effects. Considering that many anti-cancer agents have side effects, including immunosuppression, it is important to check if disulfiram has some cytotoxicity to immune cells. In this study, mouse spleen cells were treated with disulfiram and the metabolic activity was measured. Disulfiram increased the cell death of spleen cells according to annexin V-FITC/PI staining analysis. In addition, disulfiram decreased the mitochondrial membrane potential of spleen cells. The toxicity of disulfiram was concentration dependent. Interestingly, disulfiram affected the population of lymphocytes and the subset of spleen cells was altered. This study provides clinicians and researchers with valuable information regarding the toxicity of disulfiram to mouse spleen cells, particularly lymphocytes.

• Journal of Life Science
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• v.16 no.6
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• pp.964-971
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• 2006

The cancer cells, characterized by local invasion and distant metastasis, are very dependant on extracellular matrix. The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. Among the human MMPs, matirx metalloproteinase-2 (MMP-2) and matrix metalloproteinse-9 (MMP-9) are key enzymes that degrade type IV collagen of the matrix. Here, we studied the effect of disulfiram, an anti-tumor compound, on the suppression of the tumor invasion and the activity of MMP-2, MMP-9 in human osteosarcoma cells (U2OS). Disulfiram had the type IV collagenase inhibitory activity, the effect of inhibition of gene and protein expression, and these inhibitions were responsible for blocking invasion through cell mediated and non-cell mediated pathways. In conclusion, disulfiram inhibited expression of MMP-2 and MMP-9, and regulated the invasion of U2OS, Caki-1 and Caski. These observations raise the possibility of clinical therapeutic applications for disulfiram used as a potential inhibitor of cancer invasion.

• Archives of Plastic Surgery
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• v.41 no.5
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• pp.571-575
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• 2014

Background Disulfiram implantation is a widely used treatment alternative for alcohol abuse, yet reports on the surgical aspect of disulfiram implantation with respect to patient and drug-related treatment efficacy and wound complications are very limited. We present our clinical experiences with disulfiram implantation and discuss the surgical outcomes obtained with different anatomical planes for implantation. Methods Medical records of all patients referred to our clinic from the psychiatry department between 2007 and 2013 for disulfiram implantation were retrospectively analyzed. Implantation was carried out using 10 sterile Disulfiram tablets (WZF Polfa S.A.), each tablet containing 100 mg of disulfiram. The procedure was carried out by implanting the tablets randomly in either a subcutaneous or an intramuscular plane. The location and the plane of implantation and the complications were recorded for each patient and compared to determine the differences in the outcomes. Results A total of 32 implantation procedures were evaluated for this study. Twenty-five implants were placed in the intramuscular plane (78.2%), while seven implants were placed subcutaneously (21.8%). Exposure was encountered in three of the seven subcutaneous implants (42.9%), while no exposure was seen with the intramuscular implants. Incomplete absorption of the tablets was encountered in one patient with a previous subcutaneous implant who presented 1 year later for re-implantation as part of the continuation of therapy. Conclusions To overcome the issue of treatment continuation in the case of disulfiram therapy, which may be ceased due to frequently encountered wound complications, we believe that implantation in the subscapular intramuscular plane allows both uneventful healing and an out-of-reach implant location.

• Journal of The Korean Society of Clinical Toxicology
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• v.2 no.1
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• pp.54-57
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• 2004

Disulfiram (tetraethylthiuram disulphid) is used in the treatment of chronic alcoholism since it causes an unpleasant aversive reaction to alcohol. It works by inactivating hepatic aldehyde dehydrogenase, leading to pronounced rise in the acetaldehyde concentration when ethanol is metabolized. Acetaldehyde causes alcohol sensitivity, which involve vasodilation associated with feeling of hotness and facial flushing, increased heart rate and respiration rates, lowered blood pressure, nausea, headache. One of its metabolites, diethyldithiocarbamate (DDC) can inhibit the enzyme dopamine $\beta$-hydroxylase (DBH), this may account for the profound refractory hypotension and hypothermia seen with the disulfiram-ethanol reaction (DER), resulting from norepinephrine depletion. This report is presents the case of a patient we met, who presented with hypothermia caused by the disulfiram-ethanol reaction, and along with a brief review of the subject.

• Animal cells and systems
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• v.16 no.6
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• pp.462-468
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• 2012

Urodeles including newt and salamander have remarkable regenerative capacity during the postembryonic life span. Some of the unique features are the formation of the well-developed wound epidermis and the active dedifferentiation process in the early phase of regeneration. These are regarded as key events for the successful regeneration since no further regenerative activity is possible without them. In this study, we investigated the role of retinoic acid (RA) in salamander limb regeneration by blocking RA synthesis using disulfiram, an inhibitor of aldehyde dehydrogenase that oxidizes retinal to RA. Disulfiram treatment resulted in delaying the limb regeneration processes via inhibition of wound epidermis formation and dedifferentiation process. When RA was administered after disulfiram treatment, the inhibitory effect of disulfiram was rescued. In addition, disulfiram treatment after the dedifferentiation stage resulted in the mild retardation of limb regeneration, suggesting that RA might also be involved in the blastema outgrowth. Furthermore, salamander MMP-9 gene expression was also inhibited by disulfiram treatment. Collectively, our findings indicate that endogenous RA may play an important role(s) in the early phase of limb regeneration by regulating the expression of molecules responsible for the modification of intracellular and extracellular environment during salamander limb regeneration.

• BMB Reports
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• v.40 no.6
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• pp.1069-1076
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• 2007

Cancer cells, characterized by local invasion and distant metastasis, are very much dependant on the extracellular matrix. The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. In this study, we reported the effects of disulfiram, a clinically used anti-alcoholism drug, on tumor invasion suppression, as well as its effects on the activity of MMP-2 and MMP-9 in human osteosarcoma cells (U2OS). Disulfiram has been used for alcohol aversion therapy. However, recent reports have shown that disulfiram may have potential in the treatment of human cancers. Herewith, we showed that the anti-tumor effects of disulfiram, in an invasion assay using U2OS cells and that disulfiram has a type IV collagenase inhibitory activity that inhibits expression of genes and proteins responsible for both cell and non-cell mediated invasion on pathways. In conclusion, disulfiram inhibited expression of MMP-2 and MMP-9 and it regulated the invasion of human osteosarcoma cells. These observations raise the possibility of disulfiram being used clinical for the inhibition of cancer invasion.

• Korean Journal of Veterinary Research
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• v.59 no.4
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• pp.195-199
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• 2019

Disulfiram (DSF) is a member of the dithiocarbamate family that can bind copper. Recent studies have shown that DSF has anti-cancer activities, but the mechanism has not been clarified. Therefore, it is important to study the action mechanism of DSF to maximize its anticancer effects. A human leukemia cell line, HL-60, was used in this study. HL-60 cells were treated with DSF and the cellular metabolic activity was measured. DSF increased the cell death of HL-60 cells in annexin V-fluorescein isothiocyanate/propidium iodide staining analysis. In addition, DSF decreased the mitochondrial membrane potential (MMP) of the HL-60 cells. The cytotoxicity of DSF on HL-60 cells was observed at 0.4 μM. Interestingly, the reduction of MMP by DSF was recovered by N-acetyl-L-cysteine, an inhibitor of reactive oxygen species (ROS) production. This suggests that the decrease in MMP by DSF is closely related to the production of ROS in HL-60 cells, which indicates the relationship between the apoptosis of HL-60 cells by DSF and the role of the mitochondria. This study provides clinicians and researchers with valuable information regarding the anti-cancer activity of DSF in terms of the action mechanism.

• Korean Journal of Veterinary Research
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• v.62 no.1
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• pp.3.1-3.7
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• 2022

Disulfiram (DSF) is a marketed drug to treat patients with alcohol dependence by inhibiting aldehyde dehydrogenase. Over the last few decades, DSF has been shown to have anticancer effects through different mechanisms. Moreover, this effect can be elevated when used with copper (Cu). Subsequent studies have been conducted on various cancers, but few on lymphoma. This study investigated the anticancer effects of DSF on lymphoma and how this effect changed when treated with Cu. DSF synergistically decreased the metabolic activity of EL4 lymphoma cells when combined with Cu. At 1 µM of DSF alone, the metabolic activity of EL4 cells decreased by 49% compared to the control, whereas it decreased by 87% with a DSF + CuCl₂ treatment. Rhodamine 123 and 2',7'-dichlorofluorescein diacetate staining showed that DSF induced the reduction of the mitochondrial membrane potential and promoted the production of reactive oxygen species. In particular, the combined treatment of DSF + Cu induced cell death based on multiple assays, including annexin V-fluorescein isothiocyanate/propidium iodide staining. Overall, DSF has anticancer effects on lymphoma cells and exhibits synergistic effects when combined with Cu. This study provides some valuable information to broaden the use of DSF in clinics and basic research.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.3
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• pp.157-164
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• 2022

Disulfiram (DSF) is an aldehyde dehydrogenase inhibitor. DSF has potent anti-cancer activity for solid and hematological malignancies. Although the effects on cancer cells have been proven, there have been few studies on DSF toxicity in bone marrow cells (BMs). DSF reduces the metabolic activity and the mitochondrial membrane potential of BMs. In subset analyses, we confirmed that DSF does not affect the proportion of BMs. In addition, DSF significantly impaired the metabolic activity and differentiation of BMs treated with granulocyte macrophage-colony stimulating factor, an essential growth and differentiation factor for BMs. To measure DSF toxicity in BMs in vivo, mice were injected with 50 mg/kg, a dose used for anti-cancer effects. DSF did not significantly induce BM toxicity in mice and may be tolerated by antioxidant defense mechanisms. This is the first study on the effects of DSF on BMs in vitro and in vivo. DSF has been widely studied as an anti-cancer drug candidate, and many anti-cancer drugs lead to myelosuppression. In this regard, this study can provide useful information to basic science and clinical researchers.