Korean J Vet Res.  2019 Dec;59(4):195-199. 10.14405/kjvr.2019.59.4.195.

Anti-tumor activity and mitochondrial stability of disulfiram in HL-60 cells

Abstract

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.


MeSH Terms

Acetylcysteine
Apoptosis
Cell Death
Cell Line
Copper
Disulfiram*
HL-60 Cells*
Humans
Leukemia
Membrane Potential, Mitochondrial
Mitochondria
Reactive Oxygen Species
Acetylcysteine
Copper
Disulfiram
Reactive Oxygen Species
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