Dioscin Inhibits the Invasion and Migration of Hepatocellular Carcinoma HepG2 Cells by Reversing TGF-β1-Induced Epithelial-Mesenchymal Transition.

Bonan Chen,Yujuan Zhan,Shikun Zhou,Kun Wang,Yu Hou,Qiqi Liang,Weizhen Ao,Pingping Zhu,Jianyong Xiao,Junzi Ke,Xianli Wei

doi:10.3390/molecules24122222

Abstract

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.

Highlights

Dioscin is a natural steroidal saponin, one class of saponins in which the aglycone moiety is a steroid [1]
Because we aimed to examine the effects of dioscin on metastasis of HepG2 cells, we selected the less cytotoxic concentrations of dioscin (0.5, 1, 2 μM) to treat HepG2 cells for subsequent experiments
We report that dioscin inhibits the epithelial-mesenchymal transition (EMT) of HepG2 cells

Summary

Introduction

Dioscin is a natural steroidal saponin, one class of saponins in which the aglycone moiety is a steroid [1]. It is a derivative of diosgenin, whose position 3 was attached by a spirostanyl glycoside that consists of the trisaccharide alpha-L-Rha-(1->4)-[alpha-L-Rha-(1->2)]-beta-D-Glc via a glycosidic linkage [2]. Molecules 2019, 24, 2222 dioscin had an anticancer effect on a variety of cancer cells such as human leukemia K562, human lung cancer A549, and hepatocellular carcinoma Huh7 [1]. The effect of dioscin on the epithelial-mesenchymal transition (EMT) of HepG2 cells is still lacking. We discovered that dioscin can inhibit the TGF-β1-induced EMT in HepG2 cells, and the mechanisms of actions remain to be elucidated

Objectives

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Conclusion