2. Academic Validation
  3. Deubiquitylatinase inhibitor b-AP15 induces c-Myc-Noxa-mediated apoptosis in esophageal squamous cell carcinoma

Deubiquitylatinase inhibitor b-AP15 induces c-Myc-Noxa-mediated apoptosis in esophageal squamous cell carcinoma

  • Apoptosis. 2019 Oct;24(9-10):826-836. doi: 10.1007/s10495-019-01561-9.
Beibei Sha 1 2,  Xiaoyu Chen 1 2,  Han Wu 1 2,  Miaomiao Li 1 2,  Jianxiang Shi 3,  Longhao Wang 1 2,  Xingge Liu 1 2,  Ping Chen 1 2,  Tao Hu 4 5,  Pei Li 6 7
Affiliations

Affiliations

  • 1 College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
  • 2 Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, 450001, China.
  • 3 Precision Medicine Center, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450052, China.
  • 4 College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China. hnhutao@zzu.edu.cn.
  • 5 Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, 450001, China. hnhutao@zzu.edu.cn.
  • 6 College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China. lipeifreemai@zzu.edu.cn.
  • 7 Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, 450001, China. lipeifreemai@zzu.edu.cn.
PMID: 31342239 DOI: 10.1007/s10495-019-01561-9
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.

Keywords

Apoptosis; Esophagus squamous cell carcinoma; Noxa; b-AP15; c-Myc.

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