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Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4

Z. Skrott, M. Mistrik, KK. Andersen, S. Friis, D. Majera, J. Gursky, T. Ozdian, J. Bartkova, Z. Turi, P. Moudry, M. Kraus, M. Michalova, J. Vaclavkova, P. Dzubak, I. Vrobel, P. Pouckova, J. Sedlacek, A. Miklovicova, A. Kutt, J. Li, J. Mattova, C....

. 2017 ; 552 (7684) : 194-199. [pub] 20171206

Jazyk angličtina Země Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22008063

Grantová podpora
R01 CA164803 NCI NIH HHS - United States
Howard Hughes Medical Institute - United States
NV16-32030A MZ0 CEP - Centrální evidence projektů

Digitální knihovna NLK
Plný text - Článek

E-zdroje Online Plný text

NLK Nature Journals Online od 1997
Nature Journal Archive od 1997
ProQuest Central od 1990-01-04 do Před 1 rokem
Nursing & Allied Health Database (ProQuest) od 1990-01-04 do Před 1 rokem
Health & Medicine (ProQuest) od 1990-01-04 do Před 1 rokem
Psychology Database (ProQuest) od 1990-01-04 do Před 1 rokem
Public Health Database (ProQuest) od 1990-01-04 do Před 1 rokem

Odkazy

PubMed 29211715
DOI 10.1038/nature25016
Knihovny.cz E-zdroje

Cancer incidence is rising and this global challenge is further exacerbated by tumour resistance to available medicines. A promising approach to meet the need for improved cancer treatment is drug repurposing. Here we highlight the potential for repurposing disulfiram (also known by the trade name Antabuse), an old alcohol-aversion drug that has been shown to be effective against diverse cancer types in preclinical studies. Our nationwide epidemiological study reveals that patients who continuously used disulfiram have a lower risk of death from cancer compared to those who stopped using the drug at their diagnosis. Moreover, we identify the ditiocarb-copper complex as the metabolite of disulfiram that is responsible for its anti-cancer effects, and provide methods to detect preferential accumulation of the complex in tumours and candidate biomarkers to analyse its effect on cells and tissues. Finally, our functional and biophysical analyses reveal the molecular target of disulfiram's tumour-suppressing effects as NPL4, an adaptor of p97 (also known as VCP) segregase, which is essential for the turnover of proteins involved in multiple regulatory and stress-response pathways in cells.

Citace poskytuje Crossref.org

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