Dioscin Inhibits Ubiquitin-Proteasome System in Cancer Cells
10.3971/j.issn.1000-8578.2023.23.0326
- VernacularTitle:薯蓣皂苷靶向泛素-蛋白酶体的抗肿瘤活性研究
- Author:
Xinru LI
1
;
Jiaqi WANG
;
Xisong KE
;
Xianglian ZHOU
Author Information
1. Center for Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Publication Type:Research Article
- Keywords:
Ubiquitin-proteasome;
Dioscin;
Inhibitor;
Deubiquitinating enzyme;
Antitumor compound
- From:
Cancer Research on Prevention and Treatment
2023;50(6):567-572
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the antitumor small molecules targeting the ubiquitin–proteasome system (UPS) on the basis of active molecules from traditional Chinese medicine. Methods UbG76V-GFP stably expressing cell line was constructed to screen novel small molecule inhibitors targeting UPS. The fluorogenic substrates of Suc-LLVY-AMC, Z-LLE-AMC, and Boc-LRR-AMC were used to assess the effect of dioscin on the 20S proteasome hydrolase activity. The Ub-AMC substrate was used to evaluate the effect of dioscin on the intracellular deubiquitinating enzyme activity. Western blot was used to detect the effect of dioscin on intracellular ubiquitination levels. CCK-8 and colony formation assays were used to detect the inhibitory effect of dioscin on the tumor cell proliferation. Results Dioscin is a UPS inhibitor discovered through the UbG76V-GFP reporter system. It enhances intracellular ubiquitination and inhibits tumor cell proliferation and colony formation by targeting deubiquitinating enzymes. Conclusion Dioscin could significantly inhibit tumor cell proliferation by targeting ubiquitin–proteasome.
