{"entity": "publication", "iuid": "e76fe6005a4849ed99b9e64b55342a2d", "timestamp": "2026-08-26T23:25:10.261Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e76fe6005a4849ed99b9e64b55342a2d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e76fe6005a4849ed99b9e64b55342a2d"}}, "title": "Disulfiram's anti-cancer activity reflects targeting NPL4, not inhibition of aldehyde dehydrogenase.", "authors": [{"family": "Skrott", "given": "Zdenek", "initials": "Z"}, {"family": "Majera", "given": "Dusana", "initials": "D"}, {"family": "Gursky", "given": "Jan", "initials": "J", "orcid": "0000-0002-5761-7066", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e6c2eb2724144401b00a5b0c21fbfa38.json"}}, {"family": "Buchtova", "given": "Tereza", "initials": "T"}, {"family": "Hajduch", "given": "Marian", "initials": "M", "orcid": "0000-0002-4834-908X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fc2ce16232a24979a6e2a18b154fbc13.json"}}, {"family": "Mistrik", "given": "Martin", "initials": "M"}, {"family": "Bartek", "given": "Jiri", "initials": "J"}], "type": "journal article", "published": "2019-10-00", "journal": {"title": "Oncogene", "issn": "1476-5594", "volume": "38", "issue": "40", "pages": "6711-6722", "issn-l": "0950-9232"}, "abstract": "Aldehyde dehydrogenase (ALDH) is a proposed biomarker and possible target to eradicate cancer stem cells. ALDH inhibition as a treatment approach is supported by anti-cancer effects of the alcohol-abuse drug disulfiram (DSF, Antabuse). Given that metabolic products of DSF, rather than DSF itself inhibit ALDH in vivo, and that DSF's anti-cancer activity is potentiated by copper led us to investigate the relevance of ALDH as the suggested molecular cancer-relevant target of DSF. Here we show that DSF does not directly inhibit ALDH activity in diverse human cell types, while DSF's in vivo metabolite, S-methyl-N,N-diethylthiocarbamate-sulfoxide inhibits ALDH activity yet does not impair cancer cell viability. Our data indicate that the anti-cancer activity of DSF does not involve ALDH inhibition, and rather reflects the impact of DSF's copper-containing metabolite (CuET), that forms spontaneously in vivo and in cell culture media, and kills cells through aggregation of NPL4, a subunit of the p97/VCP segregase. We also show that the CuET-mediated, rather than any ALDH-inhibitory activity of DSF underlies the preferential cytotoxicity of DSF towards BRCA1- and BRCA2-deficient cells. These findings provide evidence clarifying the confusing literature about the anti-cancer mechanism of DSF, a drug currently tested in clinical trials for repositioning in oncology.", "doi": "10.1038/s41388-019-0915-2", "pmid": "31391554", "labels": [], "xrefs": [{"db": "pii", "key": "10.1038/s41388-019-0915-2"}], "notes": [], "created": "2026-08-20T08:48:17.365Z", "modified": "2026-08-20T08:48:17.462Z"}