Antrodin C Inhibits Epithelial-to-Mesenchymal Transition and Metastasis of Breast Cancer Cells via Suppression of Smad2/3 and β-Catenin Signaling Pathways

• Published in: PloS one Vol. 10; no. 2; p. e0117111
• Main Authors: Kumar, K. J. Senthil, Vani, M. Gokila, Chueh, Pin-Ju, Mau, Jeng-Leun, Wang, Sheng-Yang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.02.2015; Public Library of Science (PLoS)
• Subjects: Actin; Actin Cytoskeleton - drug effects; Actin Cytoskeleton - metabolism; Agricultural biotechnology; Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Antrodia - chemistry; Antrodia - metabolism; Antrodia cinnamomea; Breast cancer; Breast carcinoma; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cadherins - metabolism; Cancer; Cell adhesion & migration; Cell Movement - drug effects; Cell Survival - drug effects; Chemical agents; Chemotherapy; Cytoskeleton; Down-Regulation - drug effects; E-cadherin; Epithelial-Mesenchymal Transition - drug effects; Extracellular matrix; Female; Food; Food production; Gelatinase A; Humans; Insulin-like growth factors; Kinases; Maleimides - chemistry; Maleimides - isolation & purification; Maleimides - pharmacology; Markers; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; MCF-7 Cells; Mesenchyme; Metastases; Metastasis; N-Cadherin; Natural & organic foods; R&D; Regulators; Research & development; Signal transduction; Signal Transduction - drug effects; Signaling; Smad protein; Smad2 protein; Smad2 Protein - metabolism; Smad3 protein; Smad3 Protein - metabolism; Transforming Growth Factor beta1 - pharmacology; Transforming growth factor-b1; Tumors; U-Plasminogen activator; Up-Regulation - drug effects; Urokinase; Vimentin; Womens health; β-Catenin; United States > US; Taiwan; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0117111

Epithelial-to-mesenchymal transition (EMT) is a crucial event involved metastasis of certain tumors. Thus, identifying chemical agents that can block EMT is highly warranted for the development of anti-cancer chemoprevention/chemotherapies. In this study, we found that Antrodin C (ADC), a maleimide derivative isolated from Antrodia cinnamomea health food product inhibits TGF-β1-induced EMT and breast cancer cell metastasis in vitro. Pretreatment of MCF-7 cells with ADC significantly blocked TGF-β1-induced phenotypic changes and actin cytoskeleton remodeling. In addition, ADC was able to up-regulate epithelial markers such as E-cadherin and occludin, whereas mesenchymal markers including N-cadherin and vimentin were significantly inhibited, possibly through the modulation of transcriptional regulators Smad/Smad3. ADC blocked TGF-β1-induced migration and invasion of MCF-7 cells through the down-regulation of matrix-metalloproteinases (MMP-2, -9) and urokinase plasminogen activator (uPA). The inhibition of MMPs and uPA activity by ADC was reasoned by suppression of its corresponding transcription factor β-catenin. Taken together, our data suggested that ADC attenuates the TGF-β1-induced EMT, migration and invasion of human breast carcinoma through the suppression of Smad2/3 and β-catenin signaling pathways.