Repurposing an antidandruff agent to treating cancer: zinc pyrithione inhibits tumor growth via targeting proteasome-associated deubiquitinases.

ABSTRACT: 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, resulti

SUBMITTER: Zhao C 

PROVIDER: S-EPMC5355152 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature