Platycodin-D exerts its anti-cancer effect by promoting c-Myc protein ubiquitination and degradation in gastric cancer

Frontiers in Pharmacology

Pharmacology

Yancheng Tang¹  Zhonglan Wang²  Qianqian Xu²  Jiang-Jiang Qin³  Guangzhao Pan⁴  Jinyun Dong⁴  Lingling Wang⁵ 

[1] School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China;School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China;Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China;School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China;Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China;Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China;Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China;Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China;Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China;School of Life Sciences, Tianjin University, Tianjin, China;

关键词: Platycodin D;    c-Myc;    ubiquitination;    cell apoptosis;    gastric cancer;   

DOI  :  10.3389/fphar.2023.1138658

 received in 2023-01-06, accepted in 2023-02-23,  发布年份 2023

来源: Frontiers

【 摘 要 】

Platycodin D (PD) is a triterpene saponin extracted from the root of Platycodon grandiflorum. It has been reported to exhibit multiple pharmacological and biological properties. There is substantial evidence to support that PD displays a wide range of anti-tumor activities. However, the detailed molecular mechanism still needs further elaboration. In the present study, to explore whether PD inhibits gastric cancer (GC) cell viability, eight GC cell lines and the GES-1 cell line (a gastric mucosal cell line) were tested. We found that PD exhibited better inhibitory activity on GC cell lines than on the non-tumor cell line. Besides, treatment with PD led to a significant cell cycle arrest, thereby causing subsequent apoptosis. Regarding the cell growth inhibition mechanism, PD can downregulate the protein level of c-Myc rather than its mRNA level in a dose-dependent manner. Further studies revealed that PD disturbed the overall ubiquitination level in GC cell lines and enhanced the ubiquitination-dependent degradation of c-Myc. Interestingly, the inhibition of cell viability by PD could be restored to a certain extent when the expression of c-Myc was recovered, suggesting that PD-mediated GC cell growth inhibition is closely associated with c-Myc expression. Our study proposes a novel molecular mechanism for PD inhibiting GC cell proliferation and growth by destabilizing the c-Myc protein. This work may lay a preliminary foundation for developing PD as an anti-cancer therapy.

【 授权许可】

Unknown   
Copyright © 2023 Xu, Pan, Wang, Wang, Tang, Dong and Qin.