title: Lichen secondary metabolites in Flavocetraria cucullata exhibit anti-cancer effects on human cancer cells through the induction of apoptosis and suppression of tumorigenic potentials.
abstract: Lichens are symbiotic organisms which produce distinct secondary metabolic products. In the present study, we tested the cytotoxic activity of 17 lichen species against several human cancer cells and further investigated the molecular mechanisms underlying their anti-cancer activity. We found that among 17 lichens species, F. cucullata exhibited the most potent cytotoxicity in several human cancer cells. High performance liquid chromatography analysis revealed that the acetone extract of F. cucullata contains usnic acid, salazinic acid, Squamatic acid, Baeomycesic acid, d-protolichesterinic acid, and lichesterinic acid as subcomponents. MTT assay showed that cancer cell lines were more vulnerable to the cytotoxic effects of the extract than non-cancer cell lines. Furthermore, among the identified subcomponents, usnic acid treatment had a similar cytotoxic effect on cancer cell lines but with lower potency than the extract. At a lethal dose, treatment with the extract or with usnic acid greatly increased the apoptotic cell population and specifically activated the apoptotic signaling pathway; however, using sub-lethal doses, extract and usnic acid treatment decreased cancer cell motility and inhibited in vitro and in vivo tumorigenic potentials. In these cells, we observed significantly reduced levels of epithelial-mesenchymal transition (EMT) markers and phosphor-Akt, while phosphor-c-Jun and phosphor-ERK1/2 levels were only marginally affected. Overall, the anti-cancer activity of the extract is more potent than that of usnic acid alone. Taken together, F. cucullata and its subcomponent, usnic acid together with additional component, exert anti-cancer effects on human cancer cells through the induction of apoptosis and the inhibition of EMT.
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: Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Somy
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Korean Lichen Research Institute, Sunchon National University, Sunchon, Republic of Korea.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Republic of Korea.
authors.forename: Ho-Bin
authors.initials: HB
authors.lastname: Lee
authors.affiliation: Korean Lichen Research Institute, Sunchon National University, Sunchon, Republic of Korea.
authors.forename: Soonok
authors.initials: S
authors.lastname: Oh
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: College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Republic of Korea.
authors.forename: Jong-Jin
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Republic of Korea.
authors.forename: Sung-Tae
authors.initials: ST
authors.lastname: Yee
authors.affiliation: Department of Taxonomy and Ecology, Faculty of Biology and Geology, Babes'-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: Cheol
authors.initials: C
authors.lastname: Moon
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: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001572:Benzofurans / Q000494:pharmacology; D063646:Carcinogenesis / Q000187:drug effects / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D008011:Lichens / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D064210:Secondary Metabolism / Q000187:drug effects*
chemical_list: D017304:Annexin A5; D000970:Antineoplastic Agents; D001572:Benzofurans; C073339:usnic acid; D051057:Proto-Oncogene Proteins c-akt