title: Carnosic acid inhibits the epithelial-mesenchymal transition in B16F10 melanoma cells: a possible mechanism for the inhibition of cell migration.
abstract: Carnosic acid is a natural benzenediol abietane diterpene found in rosemary and exhibits anti-inflammatory, antioxidant, and anti-carcinogenic activities. In this study, we evaluated the effects of carnosic acid on the metastatic characteristics of B16F10 melanoma cells. When B16F10 cells were cultured in an in vitro Transwell system, carnosic acid inhibited cell migration in a dose-dependent manner. Carnosic acid suppressed the adhesion of B16F10 cells, as well as the secretion of matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1, urokinase plasminogen activator (uPA), and vascular cell adhesion molecule (VCAM)-1. Interestingly, secretion of TIMP-2 increased significantly in B16F10 cells treated with 10 μmol/L carnosic acid. Additionally, carnosic acid suppressed the mesenchymal markers snail, slug, vimentin, and N-cadherin and induced epithelial marker E-cadherin. Furthermore, carnosic acid suppressed phosphorylation of Src, FAK, and AKT. These results indicate that inhibition of the epithelial-mesenchymal transition may be important for the carnosic acid-induced inhibition of B16F10 cell migration.
authors.affiliation: Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyonggi-do 443-270, Korea. young0122@hallym.ac.kr.
authors.forename: So Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. hyerim0715@hallym.ac.kr.
authors.forename: Hyerim
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Food and Nutrition, Sookmyung Women's University, Seoul 140-742, Korea. mksung@sookmyung.ac.kr.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Sung
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. yhkang@hallym.ac.kr.
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Kang
authors.affiliation: Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyonggi-do 443-270, Korea. kiwon@snu.ac.kr.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyonggi-do 443-270, Korea. jyoon@hallym.ac.kr.
authors.forename: Jung Han Yoon
authors.initials: JH
authors.lastname: Park
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D045784:Abietanes; D010936:Plant Extracts; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D014157:Transcription Factors; D019010:Vascular Cell Adhesion Molecule-1; D014746:Vimentin; D011505:Protein-Tyrosine Kinases; D014568:Urokinase-Type Plasminogen Activator; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; C018381:salvin