Antrodia camphorata inhibits epithelial‐to‐mesenchymal transition by targeting multiple pathways in triple‐negative breast cancers
Authors: Hsin-Ling Yang
William Tzu-Liang Chen
You-Cheng Hseu
Jian-You Pan
Geng-Ruei Chang
Peramaiyan Rajendran
Mei-Ling Li
Jiunn-Wang Liao
Dony Chacko Mathew
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Antrodia camphorata; Twist; Wnt/β-catenin; epithelial-to-mesenchymal transition; triple-negative breast cancer.
Affiliations: Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan., Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan., Chinese Medicine Research Center, China Medical University, Taichung, Taiwan., Institute of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan., Department of Nutrition, Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan., Graduate Institute of Veterinary Pathology, National Chung Hsing University, Taichung, Taiwan., Division of Colorectal Surgery, Department of Surgery, Center of Minimally Invasive Surgery, China Medical University Hospital, China Medical University, Taichung, Taiwan., College of Medicine, China Medical University, Taichung, Taiwan.

Abstract:  Antrodia camphorata (AC) exhibits potential for engendering cell-cycle arrest as well as prompting apoptosis and metastasis inhibition in triple-negative breast cancer (TNBC) cells. We performed the current study to explore the anti-epithelial-to-mesenchymal transition (EMT) properties of fermented AC broth in TNBC cells. Our results illustrated that noncytotoxic concentrations of AC (20-60 μg/ml) reversed the morphological changes (fibroblastic-to-epithelial phenotype) as well as the EMT by upregulating the observed E-cadherin expression. Furthermore, we discovered treatment with AC substantially inhibit the Twist expression in human TNBC (MDA-MB-231) cells as well as in those that were transfected with Twist. In addition, we determined AC to decrease the observed Wnt/β-catenin nuclear translocation through a pathway determined to be dependent on GSK3β. Notably, AC treatment consistently inhibited the EMT by downregulating mesenchymal marker proteins like N-cadherin, vimentin, Snail, ZEB-1, and fibronectin; at that same time upregulating epithelial marker proteins like occludin and ZO-1. Bioluminescence imaging that was executed in vivo demonstrated AC substantially suppressed breast cancer metastasis to the lungs. Notably, we found that western blot analysis confirmed that AC decreased lung metastasis as demonstrated by upregulation of E-cadherin expression in biopsied lung tissue. Together with our results support the anti-EMT activity of AC, indicating AC as having the potential for acting as an anticancer agent for the treatment of human TNBC treatment. 

Retracted: No

PubPeer comments:
 This paper has been brought to my attention by the [Problematic Paper Screener] . * It was noted that AC treatment reduced the observed Twist expression doseu2010dependently in the derived MDAu2010MBu2010231 cells compared with the controls (Figure 4a) and 24hr treatment with AC, diminished **mRNA articulation** of Twist (Figure 4b). To the best of my knowledge, *mRNA expression* is an established term, while **mRNA articulation** is a *tortured phrase*. Additionally, could the authors explain the relation between Figures 3 and 5, some elements there being identical (marked with blue labels), others being different (marked with red labels). Of particular note is that figures under the label a4 are different, while the figures under label b4 are identical. ![file] ![file] ,