title: Inhibitory Activity of (+)-Usnic Acid against Non-Small Cell Lung Cancer Cell Motility.
abstract: Lichens are symbiotic organisms that produce various unique chemicals that can be used for pharmaceutical purposes. With the aim of screening new anti-cancer agents that inhibit cancer cell motility, we tested the inhibitory activity of seven lichen species collected from the Romanian Carpathian Mountains against migration and invasion of human lung cancer cells and further investigated the molecular mechanisms underlying their anti-metastatic activity. Among them, Alectoria samentosa, Flavocetraria nivalis, Alectoria ochroleuca, and Usnea florida showed significant inhibitory activity against motility of human lung cancer cells. HPLC results showed that usnic acid is the main compound in these lichens, and (+)-usnic acid showed similar inhibitory activity that crude extract have. Mechanistically, β-catenin-mediated TOPFLASH activity and KITENIN-mediated AP-1 activity were decreased by (+)-usnic acid treatment in a dose-dependent manner. The quantitative real-time PCR data showed that (+)-usnic acid decreased the mRNA level of CD44, Cyclin D1 and c-myc, which are the downstream target genes of both β-catenin/LEF and c-jun/AP-1. Also, Rac1 and RhoA activities were decreased by treatment with (+)-usnic acid. Interestingly, higher inhibitory activity for cell invasion was observed when cells were treated with (+)-usnic acid and cetuximab. These results implied that (+)-usnic acid might have potential activity in inhibition of cancer cell metastasis, and (+)-usnic acid could be used for anti-cancer therapy with a distinct mechanisms of action.
authors.affiliation: Korean Lichen Research Institute, Sunchon National University, Sunchon, Republic of Korea.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Korean Lichen Research Institute, Sunchon National University, Sunchon, Republic of Korea.|Faculty of Natural Science and Technology, Tay Nguyen University, Buon Ma Thuot, Vietnam.
authors.forename: Thanh Thi
authors.initials: TT
authors.lastname: Nguyen
authors.affiliation: Korean Lichen Research Institute, Sunchon National University, Sunchon, Republic of Korea.
authors.forename: Min-Hye
authors.initials: MH
authors.lastname: Jeong
authors.affiliation: Department of Taxonomy and Ecology, Faculty of Biology and Geology, Babeș-Bolyai University, Cluj-Napoca, Romania.
authors.forename: Florin
authors.initials: F
authors.lastname: Crişan
authors.affiliation: College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Republic of Korea.
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yu
authors.affiliation: College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Republic of Korea.
authors.forename: Hyung-Ho
authors.initials: HH
authors.lastname: Ha
authors.affiliation: College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Republic of Korea.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, Korea.
authors.forename: Tae Cheon
authors.initials: TC
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Chonnam National University, Gwangju, Korea.
authors.forename: Kwang Youl
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Kyung Keun
authors.initials: KK
authors.lastname: Kim
authors.affiliation: Korean Lichen Research Institute, Sunchon National University, Sunchon, Republic of Korea.
authors.forename: Jae-Seoun
authors.initials: JS
authors.lastname: Hur
authors.affiliation: College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Republic of Korea.
authors.forename: Hangun
authors.initials: H
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D001572:Benzofurans / Q000737:chemistry*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D057809:HEK293 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008011:Lichens / Q000737:chemistry*; D008175:Lung Neoplasms / Q000473:pathology*; D013058:Mass Spectrometry; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D060888:Real-Time Polymerase Chain Reaction; D012383:Romania
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; C073339:usnic acid