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Molecules 2017, 22(4), 537; doi:10.3390/molecules22040537

3,4-Dihydroxybenzalactone Suppresses Human Non-Small Cell Lung Carcinoma Cells Metastasis via Suppression of Epithelial to Mesenchymal Transition, ROS-Mediated PI3K/AKT/MAPK/MMP and NFκB Signaling Pathways

1
School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan
2
Department of Health and Nutrition Biotechnology, Asia University, Taichung 404, Taiwan
3
School of Pharmacy, College of Pharmacy, China Medical University, Taichung 404, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Nancy D. Turner
Received: 9 February 2017 / Revised: 17 March 2017 / Accepted: 20 March 2017 / Published: 28 March 2017
(This article belongs to the Collection Bioactive Compounds)
View Full-Text   |   Download PDF [15410 KB, uploaded 28 March 2017]   |  

Abstract

3,4-Dihydroxybenzalactone (DBL) was isolated from Phellinus linteus (PL), which is a folk medicine possessing various physiological effects. In this study, we used highly metastatic A549 cells to investigate efficacy of DBL inhibition of cancer metastasis and possible mechanisms. The results revealed DBL inhibited migratory and invasive abilities of cancer cells at noncytotoxic concentrations. We found DBL suppressed enzymatic activities, protein expression, and RNA levels of matrix metalloproteinase (MMP)-2 and MMP-9. Western blot results showed DBL decreased phosphoinositide 3-kinase (PI3K)/AKT, phosphorylation status of mitogen-activated protein kinases (MAPKs), and focal adhesion kinase (FAK)/paxillin, which correlated with cell migratory ability. DBL also affected epithelial to mesenchymal transition (EMT)-related biomarkers. In addition, DBL enhanced cytoprotective effects through elevated antioxidant enzymes including heme oxygenase 1 (HO-1), catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD). Moreover, DBL influenced the nuclear translocation of nuclear factor κB (NFκB), nuclear factor erythroid 2-related factor 2 (Nrf2), Snail, and Slug in A549 cells. Taken together, these results suggested that treatment with DBL may act as a potential candidate to inhibit lung cancer metastasis by inhibiting MMP-2 and -9 via affecting PI3K/AKT, MAPKs, FAK/paxillin, EMT/Snail and Slug, Nrf2/antioxidant enzymes, and NFκB signaling pathways. View Full-Text
Keywords: Phellinus linteus; DBL; cancer metastasis; MMPs; EMT; ROS Phellinus linteus; DBL; cancer metastasis; MMPs; EMT; ROS
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Chao, W.; Deng, J.-S.; Li, P.-Y.; Liang, Y.-C.; Huang, G.-J. 3,4-Dihydroxybenzalactone Suppresses Human Non-Small Cell Lung Carcinoma Cells Metastasis via Suppression of Epithelial to Mesenchymal Transition, ROS-Mediated PI3K/AKT/MAPK/MMP and NFκB Signaling Pathways. Molecules 2017, 22, 537.

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