Biomol Ther (Seoul)  
Baicalein Inhibits the Migration and Invasion of B16F10 Mouse Melanoma Cells through Inactivation of the PI3K/Akt Signaling Pathway
Eun-Ok Choi1,2, Eun-Ju Cho1, Jin-Woo Jeong2, Cheol Park3, Su-Hyun Hong4, Hye-Jin Hwang2,5, Sung-Kwon Moon6, Chang Gue Son7, Wun-Jae Kim8,* and Yung Hyun Choi2,4,*
1Department of Food and Nutrition, College of Human Ecology, Pusan National University, Busan 46241,
2Anti-Aging Research Center & Blue-Bio Industry RIC, Dongeui University, Busan 47340,
3Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dongeui University, Busan 47340,
4Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 47227,
5Department of Food and Nutrition, College of Natural Sciences and Human Ecology, Dongeui University, Busan 47340,
6Department of Food and Nutrition, Chung-Ang University, Anseong 17546,
7Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, Daejeon 34929,
8Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea
E-mail: wjkim@chungbuk.ac.kr (Kim WJ), choiyh@deu.ac.kr (Choi YH)
Tel: +82-43-269-6371 (Kim WJ), +82-51-850-7413 (Choi YH)
Fax: +82-43-269-6144 (Kim WJ), +82-51-853-4036 (Choi YH)
Received: May 3, 2016; Revised: May 26, 2016; Accepted: June 7, 2016; Published online: August 19, 2016.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Baicalein, a natural flavonoid obtained from the rhizome of Scutellaria baicalensis Georgi, has been reported to have anticancer activities in several human cancer cell lines. However, its antimetastatic effects and associated mechanisms in melanoma cells have not been extensively studied. The current study examined the effects of baicalein on cell motility and anti-invasive activity using mouse melanoma B16F10 cells. Within the noncytotoxic concentration range, baicalein significantly inhibited the cell motility and invasiveness of B16F10 cells in a concentration-dependent manner. Baicalein also reduced the activity and expression of matrix metalloproteinase (MMP)-2 and -9; however, the levels of tissue inhibitor of metalloproteinase-1 and -2 were concomitantly increased. The inhibitory effects of baicalein on cell motility and invasiveness were found to be associated with its tightening of tight junction (TJ), which was demonstrated by an increase in transepithelial electrical resistance and downregulation of the claudin family of proteins. Additionally, treatment with baicalein markedly reduced the expression levels of lipopolysaccharide-induced phosphorylated Akt and the invasive activity in B16F10 cells. Taken together, these results suggest that baicalein inhibits B16F10 melanoma cell migration and invasion by reducing the expression of MMPs and tightening TJ through the suppression of claudin expression, possibly in association with a suppression of the phosphoinositide 3-kinase/Akt signaling pathway.
Keywords: Baicalein, Migration, Invasion, PI3K/Akt, B16F10 Mouse Melanoma Cells


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