The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Drug Repurposing as an Antitumor Agent: Disulfiram-Mediated Carbonic Anhydrase 12 and Anion Exchanger 2 Modulation to Inhibit Cancer Cell Migration
Open accessAbstract
Disulfiram has been used in the treatment of alcoholism and exhibits an anti-tumor effect. However, the intracellular mechanism of anti-tumor activity of Disulfiram remains unclear. In this study, we focused on the modulatory role of Disulfiram via oncogenic factor carbonic anhydrase CA12 and its associated transporter anion exchanger AE2 in lung cancer cell line A549. The surface expression of CA12 and AE2 were decreased by Disulfiram treatment with a time-dependent manner. Disulfiram treatment did not alter the expression of Na+-bicarbonate cotransporters, nor did it affect autophagy regulation. The chloride bicarbonate exchanger activity of A549 cells was reduced by Disulfiram treatment in a time-dependent manner without change in the resting pH level. The expression and activity of AE2 and the expression of CA12 were also reduced by Disulfiram treatment in the breast cancer cell line. An invasion assay and cell migration assay revealed that Disulfiram attenuated the invasion and migration of A549 cells. In conclusion, the attenuation of AE2 and its supportive enzyme CA12, and the inhibitory effect on cell migration by Disulfiram treatment in cancer cells provided the molecular evidence supporting the potential of Disulfiram as an anticancer agent.
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“DIS modulates endogenous plasma membrane-associated carbonic anhydrases 12 (CA12) and its associated transporter anion exchanger 2 (AE2) expression while attenuating cancer cell migration and invasion through reduced AE2 activity and levels.86”
From Off-label and repurposed use of disulfiram beyond alcohol dependence: A systematic review of clinical and preclinical evidence (2026) · cites this paper as [86]
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Cites
Carbonic anhydrase inhibitors as emerging agents for the treatment and imaging of hypoxic tumors
Supuran, C. T. (2018) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2018.1548608 · Cited by 262
Švastová, E., Witarski, W., Csáderová, L., Košík, I., Škvarková, L., Hulı́ková, A., Zaťovičová, M., Baráthová, M., Kopáček, J., Pastorek, J., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.286062 · Cited by 190
Carbonic anhydrase XII functions in health and disease
Waheed, A., & Sly, W. S. (2017) · Gene · doi:10.1016/j.gene.2017.04.027 · Cited by 130
Carbonic anhydrase XII is a new therapeutic target to overcome chemoresistance in cancer cells
Kopecka, J., Campia, I., Jacobs, A., Frei, A. P., Ghigo, D., Wollscheid, B., & Riganti, C. (2015) · Oncotarget · doi:10.18632/oncotarget.2882 · Cited by 122
Parks, S. K., & Pouysségur, J. (2015) · Journal of Cellular Physiology · doi:10.1002/jcp.24930 · Cited by 110
Inhibition of Invasion and Angiogenesis by Zinc-Chelating Agent Disulfiram
Shian, S.-G., Kao, Y.-R., Wu, F. Y.-H., & Wu, C. (2003) · Molecular Pharmacology · doi:10.1124/mol.64.5.1076 · Cited by 106
Lauritzen, G., Stock, C.-M., Lemaire, J., Lund, S. F., Jensen, M. B. F., Damsgaard, B., Petersen, K. S., Wiwel, M., Rønnov‐Jessen, L., Schwab, A., et al. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.11.023 · Cited by 102
Expression of transmembrane carbonic anhydrases IX and XII in ovarian tumours
Hynninen, P., Vaskivuo, L., Saarnio, J., Haapasalo, H. K., Kivelä, J., Pastoreková, S., Pastorek, J., Waheed, A., Sly, W. S., Puistola, U., et al. (2006) · Histopathology · doi:10.1111/j.1365-2559.2006.02523.x · Cited by 101
An Agarose Spot Assay for Chemotactic Invasion
Wiggins, H. L., & Rappoport, J. Z. (2010) · BioTechniques · doi:10.2144/000113353 · Cited by 98
Cho, H.-J., Lee, T., Park, J.-B., Park, K., Choe, J., Sin, D.-I., Park, Y.-Y., Moon, Y. S., Lee, K.-G., Yeo, J., et al. (2007) · BMB Reports · doi:10.5483/bmbrep.2007.40.6.1069 · Cited by 97
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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
Metadata
- Authors
- Hwang, S., Shin, D. M., & Hong, J. H.
- Affiliations
- Gachon University (KR)
- Yonsei University (KR)
- Corresponding author
- Shin, Dong Min
- Hong, Jeong Hee
- Venue
- Molecules
- Publisher
- MDPI AG
- Published
- 2019-09-19
- Volume
- 24
- Issue
- 18
- Pages
- 3409
- ISSN
- 1420-3049 (ISSN-L)
- PMC
- PMC6767608
- OpenAlex
- W2973928408
- Cited by
- 20
- References
- 31
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 5
- FWCI
- 0.99
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Molecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Funders
- the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) and the grant from the Gachon University Gil Medical Center project (NRF-2019R1F1A1046785 (JHH), NRF-2016R1A5A2008630 (DMS), FRD 2018-07 (JHH))
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- disulfiram, drug repurposing, AE2, tumor cell migration, tumor invasion, lung cancer, breast cancer, chloride/bicarbonate exchanger, anticancer activity, A549 cells
- MeSH terms
- Antineoplastic Agents, Carbonic Anhydrases, Cell Membrane, Cell Movement, Disulfiram, Humans, Neoplasm Invasiveness, Neoplasms, Chloride-Bicarbonate Antiporters, Cell Line, Tumor, Drug Repositioning, Tumor Microenvironment
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