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Repurposing an antidandruff agent to treating cancer: zinc pyrithione inhibits tumor growth via targeting proteasome-associated deubiquitinases
The ubiquitin-proteasome system (UPS) plays a central role in various cellular processes through selectively degrading proteins involved in critical cellular functions. Targeting UPS has been validated as a novel strategy for treating human cancer, as inhibitors of the 20S proteasome catalytic activ...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355152/ https://www.ncbi.nlm.nih.gov/pubmed/28086217 http://dx.doi.org/10.18632/oncotarget.14572 |
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author | Zhao, Chong Chen, Xin Yang, Changshan Zang, Dan Lan, Xiaoying Liao, Siyan Zhang, Peiquan Wu, Jinjie Li, Xiaofen Liu, Ningning Liao, Yuning Huang, Hongbiao Shi, Xianping Jiang, Lili Liu, Xiuhua Ping, Q. Dou Wang, Xuejun Liu, Jinbao |
author_facet | Zhao, Chong Chen, Xin Yang, Changshan Zang, Dan Lan, Xiaoying Liao, Siyan Zhang, Peiquan Wu, Jinjie Li, Xiaofen Liu, Ningning Liao, Yuning Huang, Hongbiao Shi, Xianping Jiang, Lili Liu, Xiuhua Ping, Q. Dou Wang, Xuejun Liu, Jinbao |
author_sort | Zhao, Chong |
collection | PubMed |
description | The ubiquitin-proteasome system (UPS) plays a central role in various cellular processes through selectively degrading proteins involved in critical cellular functions. Targeting UPS has been validated as a novel strategy for treating human cancer, as inhibitors of the 20S proteasome catalytic activity are currently in clinical use for treatment of multiple myeloma and other cancers, and the deubiquitinase activity associated with the proteasome is also a valid target for anticancer agents. Recent studies suggested that zinc pyrithione, an FDA-approved antidandruff agent, may have antitumor activity, but the detailed molecular mechanisms remain unclear. Here we report that zinc pyrithione (ZnPT) targets the proteasome-associated DUBs (USP14 and UCHL5) and inhibits their activities, resulting in a rapid accumulation of protein-ubiquitin conjugates, but without inhibiting the proteolytic activities of 20S proteasomes. Furthermore, ZnPT exhibits cytotoxic effects against various cancer cell lines in vitro, selectively kills bone marrow cells from leukemia patients ex vivo, and efficiently inhibits the growth of lung adenocarcinoma cancer cell xenografts in nude mice. This study has identified zinc pyrithione, an FDA-approved pharmacological agent with potential antitumor properties as a proteasomal DUB inhibitor. |
format | Online Article Text |
id | pubmed-5355152 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53551522017-04-15 Repurposing an antidandruff agent to treating cancer: zinc pyrithione inhibits tumor growth via targeting proteasome-associated deubiquitinases Zhao, Chong Chen, Xin Yang, Changshan Zang, Dan Lan, Xiaoying Liao, Siyan Zhang, Peiquan Wu, Jinjie Li, Xiaofen Liu, Ningning Liao, Yuning Huang, Hongbiao Shi, Xianping Jiang, Lili Liu, Xiuhua Ping, Q. Dou Wang, Xuejun Liu, Jinbao Oncotarget Research Paper The ubiquitin-proteasome system (UPS) plays a central role in various cellular processes through selectively degrading proteins involved in critical cellular functions. Targeting UPS has been validated as a novel strategy for treating human cancer, as inhibitors of the 20S proteasome catalytic activity are currently in clinical use for treatment of multiple myeloma and other cancers, and the deubiquitinase activity associated with the proteasome is also a valid target for anticancer agents. Recent studies suggested that zinc pyrithione, an FDA-approved antidandruff agent, may have antitumor activity, but the detailed molecular mechanisms remain unclear. Here we report that zinc pyrithione (ZnPT) targets the proteasome-associated DUBs (USP14 and UCHL5) and inhibits their activities, resulting in a rapid accumulation of protein-ubiquitin conjugates, but without inhibiting the proteolytic activities of 20S proteasomes. Furthermore, ZnPT exhibits cytotoxic effects against various cancer cell lines in vitro, selectively kills bone marrow cells from leukemia patients ex vivo, and efficiently inhibits the growth of lung adenocarcinoma cancer cell xenografts in nude mice. This study has identified zinc pyrithione, an FDA-approved pharmacological agent with potential antitumor properties as a proteasomal DUB inhibitor. Impact Journals LLC 2017-01-10 /pmc/articles/PMC5355152/ /pubmed/28086217 http://dx.doi.org/10.18632/oncotarget.14572 Text en Copyright: © 2017 Zhao et al. http://creativecommons.org/licenses/by/3.0/ 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 Zhao, Chong Chen, Xin Yang, Changshan Zang, Dan Lan, Xiaoying Liao, Siyan Zhang, Peiquan Wu, Jinjie Li, Xiaofen Liu, Ningning Liao, Yuning Huang, Hongbiao Shi, Xianping Jiang, Lili Liu, Xiuhua Ping, Q. Dou Wang, Xuejun Liu, Jinbao Repurposing an antidandruff agent to treating cancer: zinc pyrithione inhibits tumor growth via targeting proteasome-associated deubiquitinases |
title | Repurposing an antidandruff agent to treating cancer: zinc pyrithione inhibits tumor growth via targeting proteasome-associated deubiquitinases |
title_full | Repurposing an antidandruff agent to treating cancer: zinc pyrithione inhibits tumor growth via targeting proteasome-associated deubiquitinases |
title_fullStr | Repurposing an antidandruff agent to treating cancer: zinc pyrithione inhibits tumor growth via targeting proteasome-associated deubiquitinases |
title_full_unstemmed | Repurposing an antidandruff agent to treating cancer: zinc pyrithione inhibits tumor growth via targeting proteasome-associated deubiquitinases |
title_short | Repurposing an antidandruff agent to treating cancer: zinc pyrithione inhibits tumor growth via targeting proteasome-associated deubiquitinases |
title_sort | repurposing an antidandruff agent to treating cancer: zinc pyrithione inhibits tumor growth via targeting proteasome-associated deubiquitinases |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355152/ https://www.ncbi.nlm.nih.gov/pubmed/28086217 http://dx.doi.org/10.18632/oncotarget.14572 |
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