, Volume 31, Issue 1, pp 29–43 | Cite as

Cadmium pyrithione suppresses tumor growth in vitro and in vivo through inhibition of proteasomal deubiquitinase

  • Xin Chen
  • Jinjie Wu
  • Qianqian Yang
  • Xiaolan Zhang
  • Peiquan Zhang
  • Siyan Liao
  • Zhimin He
  • Xuejun Wang
  • Chong Zhao
  • Jinbao Liu


The ubiquitin–proteasome system (UPS) is indispensable to the protein quality control in eukaryotic cells. Due to the remarkable clinical success of using proteasome inhibitors for clinical treatment of multiple myeloma, it is anticipated that targeting the UPS upstream of the proteasome step be an effective strategy for cancer therapy. Deubiquitinases (DUB) are proteases that remove ubiquitin from target proteins and therefore regulate multiple cellular processes including some signaling pathways altered in cancer cells. Thus, targeting DUB is a promising strategy for cancer drug discovery. Previously, we have reported that metal complexes, such as copper and gold complexes, can disrupt the UPS via suppressing the activity of 19S proteasome-associated DUBs and/or of the 20S proteasomes, thereby inducing cancer cell death. In this study, we found that cadmium pyrithione (CdPT) treatment led to remarkable accumulation of ubiquitinated proteins in cultured cancer cells and primary leukemia cells. CdPT potently inhibited the activity of proteasomal DUBs (USP14 and UCHL5), but slightly inhibited 20S proteasome activity. The anti-cancer activity of CdPT was associated with triggering apoptosis via caspase activation. Moreover, treatment with CdPT inhibited proteasome function and repressed tumor growth in animal xenograft models. Our results show that cadmium-containing complex CdPT may function as a novel proteasomal DUB inhibitor and suggest appealing prospects for cancer treatment.


Cadmium Pyrithione Proteasome Deubiquitinase Tumor 



This work was supported by the National High Technology Research and Development Program of China (2006AA02Z4B5), NSFC (81472762/H1609), MOE (20134423110002), Central Financial Grant of China (B16056001) (to J.L.), by Foundation for Young Innovative Talents of Guangdong Province (2016KQNCX136) and Guangdong Province Medical Science Research Foundation (A2017308) (to X.C.) and by US NIH R01 grants HL072166 and HL085629 (to X.W.).


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© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Protein Modification and Degradation Lab, School of Basic Medical SciencesAffiliated Tumor Hospital of Guangzhou Medical UniversityGuangzhouChina
  2. 2.Department of Pharmacy, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  3. 3.Cancer Hospital and Cancer Research InstituteGuangzhou Medical UniversityGuangzhouChina
  4. 4.Division of Basic Biomedical SciencesSanford School of Medicine of the University of South DakotaVermillionUSA
  5. 5.Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People’s HospitalGuangzhou Medical UniversityGuangzhouChina

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