Fucoidan protects hepatocytes from apoptosis and inhibits invasion of hepatocellular carcinoma by up-regulating p42/44 MAPK-dependent NDRG-1/CAP43

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 MAPKdependent NDRG-1/CAP43 and partly,under normoxic conditions,through up-regulation of p42/44MAPK-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,fucoidandisplays 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.