Inhibitory effect of fucoidan on Huh7 hepatoma cells through downregulation of CXCL12.
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 (IC50) of 2.0 and 4.0 mg/ml, respectively. alpha-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 alpha-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.
School of Health Science, Gunma University, 3-39-15 Showamachi, Maebashi, Gunma 371-8514, Japan. mine@health.gunma-u.ac.jp
Takeaki
T
Nagamine
Kou
K
Hayakawa
Takahiko
T
Kusakabe
Hisashi
H
Takada
Kyoumi
K
Nakazato
Etsuko
E
Hisanaga
Masahiko
M
Iha
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000032:analysis / Q000037:antagonists & inhibitors*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020287:In Situ Nick-End Labeling; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011134:Polysaccharides / Q000494:pharmacology*; D000509:alpha-Fetoproteins / Q000032:analysis
D000970:Antineoplastic Agents; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D011134:Polysaccharides; D000509:alpha-Fetoproteins; C007789:fucoidan