Dendritic cells resist to disulfiram-induced cytotoxicity, but reduced interleukin-12/23(p40) production
Open accessAbstract
Disulfiram (DSF), a medication for alcoholism, has recently been used as a repurposing drug owing to its anticancer effects. Despite the crucial role of dendritic cells (DCs) in immune homeostasis and cancer therapy, the effects of DSF on the survival and function of DCs have not yet been studied. Therefore, we treated bone marrow-derived DCs with DSF and lipopolysaccharide (LPS) and performed various analyses. DCs are resistant to DSF and less cytotoxic than bone marrow cells and spleen cells. The viability and metabolic activity of DCs hardly decreased after treatment with DSF in the absence or presence of LPS. DSF did not alter the expression of surface markers (MHC II, CD86, CD40, and CD54), antigen uptake capability, or the antigen-presenting ability of LPS-treated DCs. DSF decreased the production of interleukin (IL)-12/23 (p40), but not IL-6 or tumor necrosis factor-α, in LPS-treated DCs. We considered the granulocyte-macrophage colony-stimulating factor (GM-CSF) as a factor to make DCs resistant to DSF-induced cytotoxicity. The resistance of DCs to DSF decreased when GM-CSF was not given or its signaling was inhibited. Also, GM-CSF upregulated the expression of a transcription factor XBP-1 which is essential for DCs' survival. This study demonstrated for the first time that DSF did not alter the function of DCs, had low cytotoxicity, and induced differential cytokine production.
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DIS reduces IL-12/23 (p40) production of dendritic cells.
“DIS reduces IL-12/23 (p40) production of dendritic cells; it can be a treatment option for autoimmune inflammatory diseases.120”
From Off-label and repurposed use of disulfiram beyond alcohol dependence: A systematic review of clinical and preclinical evidence (2026) · cites this paper as [120]
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Benkő, B.-M., De Brito Parreirinha, N. S., Sebe, I., & Zelkó, R. (2026) · iScience · doi:10.1016/j.isci.2026.115441 · Cited by 2 · see citing works
- Authors
- Jung, H., & Joo, H.-G.
- Affiliations
- College of Veterinary Medicine, Jeju 63243, Korea
- Jeju National University (KR)
- Corresponding author
- Joo, Hong-Gu
- Venue
- The Korean Journal of Physiology & Pharmacology
- Published
- 2023-09-01
- Volume
- 27
- Issue
- 5
- Pages
- 471-479
- ISSN
- 1226-4512 (ISSN-L)
- 2093-3827
- PMC
- PMC10466071
- OpenAlex
- W4386263055
- Cited by
- 1
- References
- 26
- Citations by year
- 2026: 1
- FWCI
- 0.11
- Type
- journal article
- Language
- en
- Open access
- diamond
- dx.doi.org
- Licence
- cc-by-nc
- Locations
- Korean Journal of Physiology and Pharmacology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- disulfiram, dendritic cells, drug cytotoxicity, GM-CSF, XBP1, lipopolysaccharide, antigen presentation, drug repurposing, cancer therapy, dendritic cell survival
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