title: 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.
abstract: 3,4-Dihydroxybenzalactone (DBL) was isolated fromPhellinus 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.
authors.affiliation: School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan. sebrina0427@hotmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Chao
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung 404, Taiwan. dengjs@asia.edu.tw.
authors.forename: Jeng-Shyan
authors.initials: JS
authors.lastname: Deng
authors.affiliation: School of Pharmacy, College of Pharmacy, China Medical University, Taichung 404, Taiwan. chacolate042276@yahoo.com.tw.
authors.forename: Pei-Ying
authors.initials: PY
authors.lastname: Li
authors.affiliation: School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan. allen1987323@yahoo.com.tw.
authors.forename: Yu-Chia
authors.initials: YC
authors.lastname: Liang
authors.affiliation: School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan. gjhuang@mail.cmu.edu.tw.
authors.forename: Guan-Jhong
authors.initials: GJ
authors.lastname: Huang
mesh_terms: D000072283:A549 Cells; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism*; D009362:Neoplasm Metastasis; D000084682:Phellinus; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D007783:Lactones; D016328:NF-kappa B; C526145:Phellinus linteus extract; D010936:Plant Extracts; D017382:Reactive Oxygen Species
keywords: DBL; EMT; MMPs; Phellinus linteus; ROS; cancer metastasis