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Inhibitory Effect of Fucoidan on Huh7 Hepatoma Cells Through Downregulation of CXCL12
Authors:Takeaki Nagamine  Kou Hayakawa  Takahiko Kusakabe  Hisashi Takada  Kyoumi Nakazato  Etsuko Hisanaga
Institution:1. School of Health Science, Faculty of Medicine , Gunma University , Gunma, Japan;2. Department of Endocrinology and Metabolism , National Research Institute for Child Health and Development , Tokyo, Japan;3. Department of Medicine and Molecular Science , Gunma University Graduate School of Medicine , Gunma, Japan
Abstract:The aim of this study is to assess whether fucoidan modulates the expression of chemokine ligand 12 (CXCL12)/chemokine receptor 4 (CXCR4) and exerts antitumor activity toward Huh7 hepatoma cells. According to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, fucoidan inhibited the growth of Huh7 cells and HepG2 cells in a dose-dependent manner, with a 50% inhibition of cell growth (IC 50 ) of 2.0 and 4.0 mg/ml, respectively. α -fetoprotein levels in medium collected from fucoidan-treated cells were significantly decreased in Huh7 cells but not in HepG2 cells. Western blotting revealed that the amount of α -fetoprotein was decreased by 1.0 mg/ml of fucoidan in Huh7 cells, whereas it was unchanged in HepG2 cells. In Huh7 cells, CXCL12 mRNA expression was significantly downregulated by 1.0 mg/ml of fucoidan, whereas CXCR4 mRNA expression was unchanged by fucoidan. CXCL12 and CXCR4 mRNA were barely expressed in HepG2 cells. In addition, 1.0 mg/ml of fucoidan mildly arrested the cell cycle and induced apoptosis in Huh7 cells. The findings suggest that fucoidan exhibits antitumor activity toward Huh7 cells through the downregulation of CXCL12 expression.
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