1. Deubiquitylatinase inhibitor b-AP15 induces c-Myc-Noxa-mediated apoptosis in esophageal squamous cell carcinoma.
- Author
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Sha, Beibei, Chen, Xiaoyu, Wu, Han, Li, Miaomiao, Shi, Jianxiang, Wang, Longhao, Liu, Xingge, Chen, Ping, Hu, Tao, and Li, Pei
- Subjects
SQUAMOUS cell carcinoma ,APOPTOSIS ,CELL cycle ,PROTEOLYSIS ,CELL growth ,CELL cycle proteins - Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors in east Asia. However, the molecular mechanism underlying its progression remains unclear. The ubiquitin–proteasome system (UPS) is a central mechanism for protein degradation and turnover. Accumulating evidence showed that more and more deubiquitinases could serve as attractive anti-cancer target. The expression of USP14 and UCH37 in esophagus squamous cell carcinoma tissues were examined by immunohistochemistry and western blot assays. Effect of b-AP15, a USP14 and UCH37 inhibitor, on ESCC cell growth was evaluated by cell viability assay. After cell lines being treated with b-AP15, cell cycle, apoptosis and the expression of related proteins were further explored to investigate the anti-ESCC mechanism of b-AP15. Results showed that deubiquitinating enzymes (DUBs) USP14 and UCH37 expressed at higher levels in ESCC tissues than in adjacent tissues. b-AP15 could inhibit cell proliferation and induce G2/M cell cycle arrest and apoptosis in ESCC cells. Mechanistically, b-AP15 treatment triggered Noxa-dependent apoptosis, which was regulated by c-Myc. Silencing Noxa and c-Myc could reduce b-AP15-induced apoptosis in ESCC cells. Our results revealed a novel mechanism of anti-tumor activity of b-AP15 in ESCC, and b-AP15 could be used as a potential therapeutic agent in ESCC. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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