Dioscin Inhibits the Invasion and Migration of Hepatocellular Carcinoma HepG2 Cells by Reversing TGF-β1-Induced Epithelial-Mesenchymal Transition
Dioscin is a natural steroidal saponin that can be isolated from Chinese medicine, such as Dioscoreae rhizoma. It has wild range of pharmacological activities such as hepatoprotection, a lipid-lowering effect, and anti-inflammation. Recently, mounting studies reported the anticancer effect of diosci...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2019-06-01
|
Series: | Molecules |
Subjects: | |
Online Access: | https://www.mdpi.com/1420-3049/24/12/2222 |
id |
doaj-e121f76ab4c94a73a5eefaab47094697 |
---|---|
record_format |
Article |
spelling |
doaj-e121f76ab4c94a73a5eefaab470946972020-11-25T01:50:52ZengMDPI AGMolecules1420-30492019-06-012412222210.3390/molecules24122222molecules24122222Dioscin Inhibits the Invasion and Migration of Hepatocellular Carcinoma HepG2 Cells by Reversing TGF-β1-Induced Epithelial-Mesenchymal TransitionBonan Chen0Shikun Zhou1Yujuan Zhan2Junzi Ke3Kun Wang4Qiqi Liang5Yu Hou6Pingping Zhu7Weizhen Ao8Xianli Wei9Jianyong Xiao10Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaResearch Center of Integrative Medicine, School of Basic medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaDepartment of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaResearch Center of Integrative Medicine, School of Basic medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaDepartment of Pathology, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaResearch Center of Integrative Medicine, School of Basic medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaResearch Center of Integrative Medicine, School of Basic medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaResearch Center of Integrative Medicine, School of Basic medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaResearch Center of Integrative Medicine, School of Basic medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaDepartment of Medical Instruments, Guangdong Food and Drug Vocational College, Guangzhou 510006, ChinaDepartment of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaDioscin is a natural steroidal saponin that can be isolated from Chinese medicine, such as Dioscoreae rhizoma. It has wild range of pharmacological activities such as hepatoprotection, a lipid-lowering effect, and anti-inflammation. Recently, mounting studies reported the anticancer effect of dioscin on a variety of tumor cells. However, the potential effect of dioscin on the epithelial-mesenchymal transition (EMT) of HepG2 cells is unclear. In the present study, dioscin was identified to inhibit transforming growth factor-β1 (TGF-β1) and induced invasive and migratory behavior of HepG2 cells. Consistently, the expression of the epithelial marker E-cadherin and gap junction proteins increased following dioscin treatment, while mesenchymal markers decreased, including N-cadherin, Vimentin, Snail, and Slug. Furthermore, we discovered that TGF-β1 induces phosphorylation of JNK, p38, and Erk, whereas the activation of these kinases was reversed by dioscin treatment in a dose-dependent manner. With the addition of Asiatic acid, a p38 activator, the inhibitory effect of dioscin on EMT was reversed. Taken together, these data indicated that dioscin inhibits EMT in HepG2 cells, which is mediated in large part by inhibition of the p38-MAPK signaling.https://www.mdpi.com/1420-3049/24/12/2222dioscinepithelial-mesenchymal transitionhepatocellular carcinoma cellsTGF-β1MAPK |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bonan Chen Shikun Zhou Yujuan Zhan Junzi Ke Kun Wang Qiqi Liang Yu Hou Pingping Zhu Weizhen Ao Xianli Wei Jianyong Xiao |
spellingShingle |
Bonan Chen Shikun Zhou Yujuan Zhan Junzi Ke Kun Wang Qiqi Liang Yu Hou Pingping Zhu Weizhen Ao Xianli Wei Jianyong Xiao Dioscin Inhibits the Invasion and Migration of Hepatocellular Carcinoma HepG2 Cells by Reversing TGF-β1-Induced Epithelial-Mesenchymal Transition Molecules dioscin epithelial-mesenchymal transition hepatocellular carcinoma cells TGF-β1 MAPK |
author_facet |
Bonan Chen Shikun Zhou Yujuan Zhan Junzi Ke Kun Wang Qiqi Liang Yu Hou Pingping Zhu Weizhen Ao Xianli Wei Jianyong Xiao |
author_sort |
Bonan Chen |
title |
Dioscin Inhibits the Invasion and Migration of Hepatocellular Carcinoma HepG2 Cells by Reversing TGF-β1-Induced Epithelial-Mesenchymal Transition |
title_short |
Dioscin Inhibits the Invasion and Migration of Hepatocellular Carcinoma HepG2 Cells by Reversing TGF-β1-Induced Epithelial-Mesenchymal Transition |
title_full |
Dioscin Inhibits the Invasion and Migration of Hepatocellular Carcinoma HepG2 Cells by Reversing TGF-β1-Induced Epithelial-Mesenchymal Transition |
title_fullStr |
Dioscin Inhibits the Invasion and Migration of Hepatocellular Carcinoma HepG2 Cells by Reversing TGF-β1-Induced Epithelial-Mesenchymal Transition |
title_full_unstemmed |
Dioscin Inhibits the Invasion and Migration of Hepatocellular Carcinoma HepG2 Cells by Reversing TGF-β1-Induced Epithelial-Mesenchymal Transition |
title_sort |
dioscin inhibits the invasion and migration of hepatocellular carcinoma hepg2 cells by reversing tgf-β1-induced epithelial-mesenchymal transition |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2019-06-01 |
description |
Dioscin is a natural steroidal saponin that can be isolated from Chinese medicine, such as Dioscoreae rhizoma. It has wild range of pharmacological activities such as hepatoprotection, a lipid-lowering effect, and anti-inflammation. Recently, mounting studies reported the anticancer effect of dioscin on a variety of tumor cells. However, the potential effect of dioscin on the epithelial-mesenchymal transition (EMT) of HepG2 cells is unclear. In the present study, dioscin was identified to inhibit transforming growth factor-β1 (TGF-β1) and induced invasive and migratory behavior of HepG2 cells. Consistently, the expression of the epithelial marker E-cadherin and gap junction proteins increased following dioscin treatment, while mesenchymal markers decreased, including N-cadherin, Vimentin, Snail, and Slug. Furthermore, we discovered that TGF-β1 induces phosphorylation of JNK, p38, and Erk, whereas the activation of these kinases was reversed by dioscin treatment in a dose-dependent manner. With the addition of Asiatic acid, a p38 activator, the inhibitory effect of dioscin on EMT was reversed. Taken together, these data indicated that dioscin inhibits EMT in HepG2 cells, which is mediated in large part by inhibition of the p38-MAPK signaling. |
topic |
dioscin epithelial-mesenchymal transition hepatocellular carcinoma cells TGF-β1 MAPK |
url |
https://www.mdpi.com/1420-3049/24/12/2222 |
work_keys_str_mv |
AT bonanchen dioscininhibitstheinvasionandmigrationofhepatocellularcarcinomahepg2cellsbyreversingtgfb1inducedepithelialmesenchymaltransition AT shikunzhou dioscininhibitstheinvasionandmigrationofhepatocellularcarcinomahepg2cellsbyreversingtgfb1inducedepithelialmesenchymaltransition AT yujuanzhan dioscininhibitstheinvasionandmigrationofhepatocellularcarcinomahepg2cellsbyreversingtgfb1inducedepithelialmesenchymaltransition AT junzike dioscininhibitstheinvasionandmigrationofhepatocellularcarcinomahepg2cellsbyreversingtgfb1inducedepithelialmesenchymaltransition AT kunwang dioscininhibitstheinvasionandmigrationofhepatocellularcarcinomahepg2cellsbyreversingtgfb1inducedepithelialmesenchymaltransition AT qiqiliang dioscininhibitstheinvasionandmigrationofhepatocellularcarcinomahepg2cellsbyreversingtgfb1inducedepithelialmesenchymaltransition AT yuhou dioscininhibitstheinvasionandmigrationofhepatocellularcarcinomahepg2cellsbyreversingtgfb1inducedepithelialmesenchymaltransition AT pingpingzhu dioscininhibitstheinvasionandmigrationofhepatocellularcarcinomahepg2cellsbyreversingtgfb1inducedepithelialmesenchymaltransition AT weizhenao dioscininhibitstheinvasionandmigrationofhepatocellularcarcinomahepg2cellsbyreversingtgfb1inducedepithelialmesenchymaltransition AT xianliwei dioscininhibitstheinvasionandmigrationofhepatocellularcarcinomahepg2cellsbyreversingtgfb1inducedepithelialmesenchymaltransition AT jianyongxiao dioscininhibitstheinvasionandmigrationofhepatocellularcarcinomahepg2cellsbyreversingtgfb1inducedepithelialmesenchymaltransition |
_version_ |
1724999974085722112 |