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Clinically used antirheumatic agent auranofin is a proteasomal deubiquitinase inhibitor and inhibits tumor growth
Proteasomes are attractive emerging targets for anti-cancer therapies. Auranofin (Aur), a gold-containing compound clinically used to treat rheumatic arthritis, was recently approved by US Food and Drug Administration for Phase II clinical trial to treat cancer but its anti-cancer mechanism is poorl...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170648/ https://www.ncbi.nlm.nih.gov/pubmed/24977961 |
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author | Liu, Ningning Li, Xiaofen Huang, Hongbiao Zhao, Chong Liao, Siyan Yang, Changshan Liu, Shouting Song, Wenbin Lu, Xiaoyu Lan, Xiaoying Chen, Xin Yi, Songgang Xu, Li Jiang, Lili Zhao, Canguo Dong, Xiaoxian Zhou, Ping Li, Shujue Wang, Shunqing Shi, Xianping Dou, Ping Q. Wang, Xuejun Liu, Jinbao |
author_facet | Liu, Ningning Li, Xiaofen Huang, Hongbiao Zhao, Chong Liao, Siyan Yang, Changshan Liu, Shouting Song, Wenbin Lu, Xiaoyu Lan, Xiaoying Chen, Xin Yi, Songgang Xu, Li Jiang, Lili Zhao, Canguo Dong, Xiaoxian Zhou, Ping Li, Shujue Wang, Shunqing Shi, Xianping Dou, Ping Q. Wang, Xuejun Liu, Jinbao |
author_sort | Liu, Ningning |
collection | PubMed |
description | Proteasomes are attractive emerging targets for anti-cancer therapies. Auranofin (Aur), a gold-containing compound clinically used to treat rheumatic arthritis, was recently approved by US Food and Drug Administration for Phase II clinical trial to treat cancer but its anti-cancer mechanism is poorly understood. Here we report that (i) Aur shows proteasome-inhibitory effect that is comparable to that of bortezomib/Velcade (Vel); (ii) different from bortezomib, Aur inhibits proteasome-associated deubiquitinases (DUBs) UCHL5 and USP14 rather than the 20S proteasome; (iii) inhibition of the proteasome-associated DUBs is required for Aur-induced cytotoxicity; and (iv) Aur selectively inhibits tumor growth in vivo and induces cytotoxicity in cancer cells from acute myeloid leukemia patients. This study provides important novel insight into understanding the proteasome-inhibiting property of metal-containing compounds. Although several DUB inhibitors were reported, this study uncovers the first drug already used in clinic that can inhibit proteasome-associated DUBs with promising anti-tumor effects. |
format | Online Article Text |
id | pubmed-4170648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-41706482014-09-22 Clinically used antirheumatic agent auranofin is a proteasomal deubiquitinase inhibitor and inhibits tumor growth Liu, Ningning Li, Xiaofen Huang, Hongbiao Zhao, Chong Liao, Siyan Yang, Changshan Liu, Shouting Song, Wenbin Lu, Xiaoyu Lan, Xiaoying Chen, Xin Yi, Songgang Xu, Li Jiang, Lili Zhao, Canguo Dong, Xiaoxian Zhou, Ping Li, Shujue Wang, Shunqing Shi, Xianping Dou, Ping Q. Wang, Xuejun Liu, Jinbao Oncotarget Research Paper Proteasomes are attractive emerging targets for anti-cancer therapies. Auranofin (Aur), a gold-containing compound clinically used to treat rheumatic arthritis, was recently approved by US Food and Drug Administration for Phase II clinical trial to treat cancer but its anti-cancer mechanism is poorly understood. Here we report that (i) Aur shows proteasome-inhibitory effect that is comparable to that of bortezomib/Velcade (Vel); (ii) different from bortezomib, Aur inhibits proteasome-associated deubiquitinases (DUBs) UCHL5 and USP14 rather than the 20S proteasome; (iii) inhibition of the proteasome-associated DUBs is required for Aur-induced cytotoxicity; and (iv) Aur selectively inhibits tumor growth in vivo and induces cytotoxicity in cancer cells from acute myeloid leukemia patients. This study provides important novel insight into understanding the proteasome-inhibiting property of metal-containing compounds. Although several DUB inhibitors were reported, this study uncovers the first drug already used in clinic that can inhibit proteasome-associated DUBs with promising anti-tumor effects. Impact Journals LLC 2014-06-18 /pmc/articles/PMC4170648/ /pubmed/24977961 Text en Copyright: © 2014 Liu et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Liu, Ningning Li, Xiaofen Huang, Hongbiao Zhao, Chong Liao, Siyan Yang, Changshan Liu, Shouting Song, Wenbin Lu, Xiaoyu Lan, Xiaoying Chen, Xin Yi, Songgang Xu, Li Jiang, Lili Zhao, Canguo Dong, Xiaoxian Zhou, Ping Li, Shujue Wang, Shunqing Shi, Xianping Dou, Ping Q. Wang, Xuejun Liu, Jinbao Clinically used antirheumatic agent auranofin is a proteasomal deubiquitinase inhibitor and inhibits tumor growth |
title | Clinically used antirheumatic agent auranofin is a proteasomal
deubiquitinase inhibitor and inhibits tumor growth |
title_full | Clinically used antirheumatic agent auranofin is a proteasomal
deubiquitinase inhibitor and inhibits tumor growth |
title_fullStr | Clinically used antirheumatic agent auranofin is a proteasomal
deubiquitinase inhibitor and inhibits tumor growth |
title_full_unstemmed | Clinically used antirheumatic agent auranofin is a proteasomal
deubiquitinase inhibitor and inhibits tumor growth |
title_short | Clinically used antirheumatic agent auranofin is a proteasomal
deubiquitinase inhibitor and inhibits tumor growth |
title_sort | clinically used antirheumatic agent auranofin is a proteasomal
deubiquitinase inhibitor and inhibits tumor growth |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170648/ https://www.ncbi.nlm.nih.gov/pubmed/24977961 |
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