Lichen secondary metabolites in Flavocetraria cucullata exhibit anti-cancer effects on human cancer cells through the induction of apoptosis and suppression of tumorigenic potentials

• Published in: PloS one Vol. 9; no. 10; p. e111575
• Main Authors: Nguyen, Thanh Thi, Yoon, Somy, Yang, Yi, Lee, Ho-Bin, Oh, Soonok, Jeong, Min-Hye, Kim, Jong-Jin, Yee, Sung-Tae, Crişan, Florin, Moon, Cheol, Lee, Kwang Youl, Kim, Kyung Keun, Hur, Jae-Seoun, Kim, Hangun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.10.2014; Public Library of Science (PLoS)
• Subjects: Acetone; Acids; Angiogenesis; Animals; Annexin A5 - metabolism; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Benzofurans - pharmacology; Biology and Life Sciences; Cancer; Cancer cells; Cancer treatment; Carcinogenesis - drug effects; Carcinogenesis - pathology; Cell Adhesion - drug effects; Cell cycle; Cell Line, Tumor; Cell Movement - drug effects; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Cell Proliferation - drug effects; Chromatography; Cytotoxicity; Exhibitions; G1 Phase - drug effects; Humans; Kinases; Lichens; Lichens - chemistry; Liquid chromatography; Lung cancer; Medical research; Medicine and Health Sciences; Metabolites; Metastasis; Mice, Inbred BALB C; Mice, Nude; National parks; Penicillin; Pharmaceutical sciences; Pharmacy; Phosphorylation - drug effects; Plant metabolites; Proteomics; Proto-Oncogene Proteins c-akt - metabolism; Secondary Metabolism - drug effects; United States > US; South Korea; Romania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0111575

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.