Abstract

Diol-type ginsenosides, such as protopanaxadiol (PPD), exhibit antioxidation, anti-inflammation, and antitumor effects. However, the antitumor effect of these ginsenosides and the mechanism of PPD remain unclear. In this work, the antitumor effects of several derivatives, including PPD, Rg5, Rg3, Rh2, and Rh3, were evaluated in five different cancer cell lines. PPD demonstrated the best inhibitory effects on the proliferation and migration of the five cancer cell lines, especially the hepatocellular carcinoma (HCC) cell lines. Therefore, the mechanism of action of PPD in HCC cells was elucidated. PPD inhibited the proliferation, migration, and invasion ability of HepG2 and PLC/PRF/5 cells in a dose-dependent manner. Western blot and immunofluorescence assay showed that PPD can alter the expression of epithelial–mesenchymal transition markers, increase E-cadherin expression, and decrease vimentin expression. Docking and biacore experiments revealed that STAT3 is the target protein of PPD, which formed hydrogen bonds with Gly583/Leu608/Tyr674 at the SH2 domain of STAT3. PPD inhibited the phosphorylation of STAT3 and its translocation from the cytosol to the nucleus, thereby inhibiting the expression of Twist1. PPD also inhibited tumor volume and tumor lung metastasis in PLC/PRF/5 xenograft model. In conclusion, PPD can inhibit the proliferation and metastasis of HCC cells through the STAT3/Twist1 pathway.

Details

Title
Protopanaxadiol inhibits epithelial–mesenchymal transition of hepatocellular carcinoma by targeting STAT3 pathway
Author
Yang, Lan 1 ; Xue-ying, Zhang 1 ; Li, Kun 1 ; An-ping, Li 2 ; Wen-dong, Yang 1 ; Yang, Ru 1 ; Wang, Peng 3 ; Zi-han, Zhao 1 ; Cui, Fang 1 ; Yuan Qin 1 ; Jia-huan, Yang 1 ; Hong-lian, Tao 1 ; Sun, Tao 1 ; Chen, Shuang 4 ; Pei-hua, Yu 5 ; Hui-juan, Liu 6 ; Cheng, Yang 1 

 State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China; Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China 
 State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China; College of Life Sciences, Nankai University, Tianjin, China 
 Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China; College of Marine and Environmental Sciences, Tianjin University of Science and Technology, Tianjin, China 
 Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China 
 Enoch Phytomedicine Ltd., Shenzhen, China 
 State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China; Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China; College of Life Sciences, Nankai University, Tianjin, China 
Pages
1-13
Publication year
2019
Publication date
Aug 2019
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2276821930
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.