Antrodia camphorata inhibits metastasis and epithelial-to-mesenchymal transition via the modulation of claudin-1 and Wnt/β-catenin signaling pathways in human colon cancer cells

You-Cheng Hseu; Yu-Hsien Chao; Kai-Yuan Lin; Tzong-Der Way; Hui-Yi Lin; Varadharajan Thiyagarajan; Hsin-Ling Yang

doi:10.1016/j.jep.2017.07.001

Antrodia camphorata inhibits metastasis and epithelial-to-mesenchymal transition via the modulation of claudin-1 and Wnt/β-catenin signaling pathways in human colon cancer cells

J Ethnopharmacol. 2017 Aug 17:208:72-83. doi: 10.1016/j.jep.2017.07.001. Epub 2017 Jul 5.

Authors

You-Cheng Hseu¹, Yu-Hsien Chao², Kai-Yuan Lin³, Tzong-Der Way⁴, Hui-Yi Lin⁵, Varadharajan Thiyagarajan⁶, Hsin-Ling Yang⁷

Affiliations

¹ Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan.
² Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan.
³ Department of Medical Research, Chi-Mei Medical Center, Tainan 710, Taiwan.
⁴ Department of Life Sciences, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan.
⁵ School of Pharmacy, College of Pharmacy, China Medical University, Taichung 40402, Taiwan.
⁶ Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan. Electronic address: varadha86@gmail.com.
⁷ Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan. Electronic address: hlyang@mail.cmu.edu.tw.

PMID: 28688953
DOI: 10.1016/j.jep.2017.07.001

Abstract

Ethnopharmacological relevance: Antrodia camphorata (AC) is a well known traditional Chinese medicinal mushroom in Taiwan, has been used to treat various diseases including cancer.

Materials and methods: In this study, we investigated the anti-metastatic and anti-EMT properties of a fermented culture broth of AC in human colon SW480^claudin-1- and metastatic SW620^claudin-1+ cancer cells in vitro.

Results: AC down-regulates claudin-1 and inhibits the proliferation and colony-formation abilities of both SW620^claudin-1+ and SW480^claudin-1- cells. In highly metastatic SW620^claudin-1+ cells, non-cytotoxic concentrations of AC significantly inhibited migration/invasion, accompanied by the down-regulation of MMP-2 and MMP-9 proteins. AC decreased nuclear translocation of Wnt/β-catenin through a GSK3β-dependent pathway. AC consistently inhibited EMT by up-regulating the epithelial and downregulating the mesenchymal marker proteins. In SW480^claudin-1- cells, AC suppressed migration/invasion potentially through the inhibition of the PI3K/AKT/NFκB signaling pathways without altering the expression levels of β-catenin and GSK3β proteins.

Conclusion: Altogether, this study demonstrates the anti-metastatic and anti-EMT activities of AC, which may contribute to the development of a chemopreventive agent for colon cancer.

Keywords: Anti-EMT; Anti-metastatic; Antrodia camphorata; Chemopreventive; Colon cancer.

MeSH terms

Animals
Antineoplastic Agents / pharmacology*
Antrodia*
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
Cell Survival / drug effects
Claudin-1 / metabolism*
Colonic Neoplasms / metabolism
Colonic Neoplasms / pathology
Epithelial-Mesenchymal Transition / drug effects*
Humans
Mice
Wnt Signaling Pathway / drug effects*

Substances

Antineoplastic Agents
Claudin-1