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

HL-60세포에서 disulfiram의 항암작용과 미토콘드리아 안정성에 대한 연구

  • Shin, Hyowon (Veterinary Medical Research Institute, College of Veterinary Medicine, Jeju National University) ;
  • Han, Yong (Veterinary Medical Research Institute, College of Veterinary Medicine, Jeju National University) ;
  • Joo, Hong-Gu (Veterinary Medical Research Institute, College of Veterinary Medicine, Jeju National University)
  • 신효원 (제주대학교 수의과대학 수의과학연구소) ;
  • 한용 (제주대학교 수의과대학 수의과학연구소) ;
  • 주홍구 (제주대학교 수의과대학 수의과학연구소)
  • Received : 2019.08.08
  • Accepted : 2019.10.29
  • Published : 2019.12.31

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.

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