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Int. J. Mol. Sci. 2014, 15(7), 12698-12713; doi:10.3390/ijms150712698

Carnosic Acid Inhibits the Epithelial-Mesenchymal Transition in B16F10 Melanoma Cells: A Possible Mechanism for the Inhibition of Cell Migration

1
Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyonggi-do 443-270, Korea
2
Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea
3
Department of Food and Nutrition, Sookmyung Women's University, Seoul 140-742, Korea
4
WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Korea
*
Authors to whom correspondence should be addressed.
Received: 16 June 2014 / Revised: 12 July 2014 / Accepted: 14 July 2014 / Published: 17 July 2014
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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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. View Full-Text
Keywords: carnosic acid; melanoma; migration; epithelial-mesenchymal transition carnosic acid; melanoma; migration; epithelial-mesenchymal transition
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MDPI and ACS Style

Park, S.Y.; Song, H.; Sung, M.-K.; Kang, Y.-H.; Lee, K.W.; Park, J.H.Y. Carnosic Acid Inhibits the Epithelial-Mesenchymal Transition in B16F10 Melanoma Cells: A Possible Mechanism for the Inhibition of Cell Migration. Int. J. Mol. Sci. 2014, 15, 12698-12713.

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