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Antrodia salmonea suppresses invasion and metastasis in triple-negative breast cancer cells by reversing EMT through the NF-κB and Wnt/β-catenin signaling pathway

Hseu, You-Cheng, Lin, Yi-Chun, Rajendran, Peramaiyan, Thigarajan, Varadharajan, Mathew, Dony Chacko, Lin, Kai-Yuan, Way, Tzong-Der, Liao, Jiunn-Wang, Yang, Hsin-Ling
Food and chemical toxicology 2019 v.124 pp. 219-230
Antrodia, Western blotting, antineoplastic activity, antineoplastic agents, beta catenin, bioluminescence, breast neoplasms, cadherins, enzyme activity, fluorescent antibody technique, fungi, image analysis, immunohistochemistry, luciferase, lungs, metastasis, mice, neoplasm cells, reverse transcriptase polymerase chain reaction, signal transduction, staining, tau-protein kinase, toxicology, transcription factor NF-kappa B, vascular endothelial growth factors, vimentin, Taiwan
Antrodia salonea (AS), a fungus that is indigenous to Taiwan has been well known for its anti-cancer properties. We investigated the anti-metastatic and anti-epithelial-mesenchymal transition (EMT) properties of AS in TNBC cells. To determine their EMT and metastasis levels, in vitro wound healing, wound invasion, Western blotting, RT-PCR, luciferase activity and immunofluorescence assays were performed, while the in vivo anti-metastatic efficacy of AS was evaluated in BALB/c-nu mice through bioluminescence imaging, HE staining, and immunohistochemical staining. MDA-MB-231 cells, when treated with AS concentrations (25–100 μg/mL) resulted in significant reduction of invasion and migration as well as the downregulation of VEGF, uPAR, uPA and MMP-9 (inhibition of PI3K/AKT/NFκB pathways). AS treatment prevented morphological changes and reversed EMT through the upregulation of E-cadherin and the downregulation of N-cadherin, Slug, Twist, and Vimentin. Inhibition of Smad3 signaling pathway, downregulation of β-catenin pathway and upregulation of GSK3β expression were also observed while, suppression of metastasis and EMT in TGF-β1-stimulated non-tumorigenic MCF-10A cells was observed when treated with AS. Histological analysis confirmed that AS reduced tumor metastasis and upregulated E-cadherin expression in biopsied lung tissues. Our results indicated that AS exhibits anti-EMT and anti-metastatic activity, that could contribute to develop anticancer drugs against TNBC.