You-Cheng Hseu1, Yu-Hsien Chao2, Kai-Yuan Lin3, Tzong-Der Way4, Hui-Yi Lin5, Varadharajan Thiyagarajan6, Hsin-Ling Yang7. 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.
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 SW480claudin-1- and metastatic SW620claudin-1+ cancer cells in vitro. RESULTS: AC down-regulates claudin-1 and inhibits the proliferation and colony-formation abilities of both SW620claudin-1+ and SW480claudin-1- cells. In highly metastatic SW620claudin-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 SW480claudin-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.
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 SW480claudin-1- and metastatic SW620claudin-1+ cancer cells in vitro. RESULTS: AC down-regulates claudin-1 and inhibits the proliferation and colony-formation abilities of both SW620claudin-1+ and SW480claudin-1- cells. In highly metastatic SW620claudin-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 SW480claudin-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.