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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00937

Arctigenin attenuates tumor metastasis through inhibiting epithelial-mesenchymal transition in hepatocellular carcinoma via suppressing GSK3β-dependent Wnt/β-catenin signaling pathway in vivo and in vitro

 Zheng Lu1, Lingling Chang1,  Hongbo Zhou2,  Xiaoqiang Liu1, Yinqian Li1, Tiejun Mi1 and  Dewen Tong1*
  • 1Northwest A&F University, China
  • 2Huazhong Agricultural University, China

Arctigenin (ARG) has been reported to be a bioactive lignan from Arctium lappa exerting various activities including anti-cancer, immune-regulation and etc. The present study aimed to investigate the anti-metastasis activity and mechanism of ARG against hepatocellular carcinoma in vitro and in vivo. The results showed that ARG exhibited a significant cytotoxicity Hep G2 and SMMC 7721 cells (but not on normal liver cells LO2). In addition, the migration and invasion of Hep G2 and SMMC 7721 cells were also remarkably repressed. Furthermore, ARG attenuated Wnt/β-catenin signaling activation, resulted in the down-regulation of β-catenin target genes including c-Myc, Cyclin D1, MMP-9 and ZO-1. Noticeably, ARG attenuated the activation of Wnt/β-catenin through a GSK3β-dependent pathway. Besides, we also found that ARG potentially inhibited epithelial-mesenchymal transition by up-regulating the epithelial and down-regulating the mesenchymal marker proteins. In vivo, intraperitoneal injection of ARG not only significantly inhibited the growth of subcutaneous transplanted tumor, but also dramatically alleviated the tumor metastasis in liver. Our data demonstrated that ARG exerted anti-epithelial-mesenchymal transition and anti-metastasis activities against hepatocellular carcinoma, which might make it a candidate as a preventive agent for cancer metastasis.

Keywords: Arctigenin, Hepatocellular Carcinoma, Anti-metastasis, anti-EMT, Wnt/β-catenin

Received: 17 Apr 2019; Accepted: 22 Jul 2019.

Edited by:

Judit Hohmann, University of Szeged, Hungary

Reviewed by:

Ali H. Eid, American University of Beirut, Lebanon
Susanne M. Henning, University of California, Los Angeles, United States  

Copyright: © 2019 Lu, Chang, Zhou, Liu, Li, Mi and Tong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Dewen Tong, Northwest A&F University, Yangling, China, dwtong@nwsuaf.edu.cn