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Original Article

Korean J Physiol Pharmacol 2022; 26(3): 157-164

Published online May 1, 2022 https://doi.org/10.4196/kjpp.2022.26.3.157

Copyright © Korean J Physiol Pharmacol.

Evaluation of the effects of disulfiram, an alcohol-aversive agent with anti-cancer activity, on mouse bone marrow cells

Seo-Ro Park1 and Hong-Gu Joo1,2,*

1College of Veterinary Medicine, 2Veterinary Medical Research Institute, Jeju National University, Jeju 63243, Korea

Correspondence to:Hong-Gu Joo
E-mail: jooh@jejunu.ac.kr

Author contributions: S.R.P. performed the experiments and wrote the manuscript. H.G.J. designed and supervised the study.

Received: March 4, 2021; Revised: November 6, 2021; Accepted: January 27, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.

Keywords: Bone marrow cells, Cell death, Disulfiram, GM-CSF, In vivo toxicity