Fucoidan protects hepatocytes from apoptosis and inhibits invasion of hepatocellular carcinoma by up-regulating p42/44 MAPK-dependent NDRG-1/CAP43.
10.1016/j.apsb.2015.09.004
- Author:
Yuri CHO
1
;
Jung-Hwan YOON
1
;
Jeong-Ju YOO
1
;
Minjong LEE
1
;
Dong Hyeon LEE
1
;
Eun Ju CHO
1
;
Jeong-Hoon LEE
1
;
Su Jong YU
1
;
Yoon Jun KIM
1
;
Chung Yong KIM
1
Author Information
1. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
- Publication Type:Journal Article
- Keywords:
BA, bile acid;
CXCL, chemokine ligand;
Cultured hepatocyte;
DISC, death-inducing signaling complex;
DMEM, Dulbecco׳s modified Eagle׳s medium;
DNA, deoxyribonucleic acid;
ELISA, enzyme-linked immunosorbent assay;
FADD, Fas associated death domain;
FBS, fetal bovine serum;
FCS, fetal calf serum;
Fucoidan;
GAPDH, glyceraldehyde-3-phosphate dehydrogenase;
GP, glypican;
HCC, hepatocellular carcinoma;
Hepatocellular carcinoma;
Hepatoprotective;
Hypoxia;
IHC, immunohistochemistry;
Invasion;
JNK, c-Jun NH2-terminal kinase;
MAPK, mitogen-activated protein kinase;
MTS, 3,4-(5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt;
NDRG, N-myc downstream-regulated gene;
NDRG-1/CAP43;
PCR, polymerase chain reaction;
RNA, ribonucleic acid;
SD, standard deviation;
SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis;
VMP, vacuole membrane protein;
VMP-1;
WME, William's medium E;
cDNA, complementary DNA;
siRNA, small interfering RNA
- From:
Acta Pharmaceutica Sinica B
2015;5(6):544-553
- CountryChina
- Language:English
-
Abstract:
Fucoidan is a traditional Chinese medicine suggested to possess anti-tumor effects. In this study the anti-metastatic effects of fucoidan were investigated in vitro in human hepatocellular carcinoma (HCC) cells (Huh-7 and SNU-761) under normoxic and hypoxic conditions and in vivo using a distant liver metastasis model involving injection of MH134 cells into spleen via the portal vein. Its ability to protect hepatocytes against bile acid (BA)-induced apoptosis was investigated in primary hepatocytes. Fucoidan was found to suppress the invasion of HCC cells through up-regulation of p42/44 MAPK-dependent NDRG-1/CAP43 and partly, under normoxic conditions, through up-regulation of p42/44 MAPK-dependent VMP-1 expression. It also significantly decreased liver metastasis in vivo. As regards its hepatoprotective effect, fucoidan decreased BA-induced hepatocyte apoptosis as shown by the attenuation of caspase-8, and -7 cleavages and suppression of the mobilization of caspase-8 and Fas associated death domain (FADD) into the death-inducing signaling complex. In summary, fucoidan displays inhibitory effects on proliferation of HCC cells and protective effects on hepatocytes. The results suggest fucoidan is a potent suppressor of tumor invasion with hepatoprotective effects.
