Polygalacin D inhibits the growth of hepatocellular carcinoma cells through BNIP3L-mediated mitophagy and endogenous apoptosis pathways.
10.1016/S1875-5364(23)60452-2
- Author:
Fulong NAN
1
;
Wenlong NAN
2
;
Zhongjie YU
1
;
Hui WANG
1
;
Xiaoni CUI
3
;
Shasha JIANG
1
;
Xianjuan ZHANG
1
;
Jun LI
1
;
Zhifei WANG
1
;
Shuyun ZHANG
1
;
Bin WANG
4
;
Yiquan LI
5
Author Information
1. Department of Special Medicine, Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao 266000, China.
2. China Animal Health and Epidemiology Center, Qingdao 266000, China.
3. Sino-Cell Biomed Co., Ltd., Qingdao 266000, China.
4. Department of Special Medicine, Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao 266000, China. Electronic address: wangbin532@126.com.
5. Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun 130000, China. Electronic address: 905381255@qq.com.
- Publication Type:Journal Article
- Keywords:
Apoptosis;
Autophagy;
Hepatocellular carcinoma;
Platycodon grandiflorum;
Polygalacin D
- MeSH:
Humans;
Mitophagy;
Carcinoma, Hepatocellular/pathology*;
Liver Neoplasms/pathology*;
Cell Line;
Autophagy;
Apoptosis;
Membrane Proteins;
Proto-Oncogene Proteins/genetics*;
Tumor Suppressor Proteins/pharmacology*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2023;21(5):346-358
- CountryChina
- Language:English
-
Abstract:
Platycodon grandiflorum (Jacq.) A. DC. is a famous medicinal plant commonly used in East Asia. Triterpene saponins isolated from P. grandiflorum are the main biologically active compounds, among which polygalacin D (PGD) has been reported to be an anti-tumor agent. However, its anti-tumor mechanism against hepatocellular carcinoma is unknown. This study aimed to explore the inhibitory effect of PGD in hepatocellular carcinoma cells and related mechanisms of action. We found that PGD exerted significant inhibitory effect on hepatocellular carcinoma cells through apoptosis and autophagy. Analysis of the expression of apoptosis-related proteins and autophagy-related proteins revealed that this phenomenon was attributed to the mitochondrial apoptosis and mitophagy pathways. Subsequently, using specific inhibitors, we found that apoptosis and autophagy had mutually reinforcing effects. In addition, further analysis of autophagy showed that PGD induced mitophagy by increasing BCL2 interacting protein 3 like (BNIP3L) levels.In vivo experiments demonstrated that PGD significantly inhibited tumor growth and increased the levels of apoptosis and autophagy in tumors. Overall, our findings showed that PGD induced cell death of hepatocellular carcinoma cells primarily through mitochondrial apoptosis and mitophagy pathways. Therefore, PGD can be used as an apoptosis and autophagy agonist in the research and development of antitumor agents.
