Hispolon Suppresses SK-Hep1 Human Hepatoma Cell Metastasis by Inhibiting Matrix Metalloproteinase-2/9 and Urokinase-Plasminogen Activator through the PI3K/Akt and ERK Signaling Pathways

Cancer metastasis is a primary cause of cancer death. Hispolon is an active phenolic compound of Phellinus linteus, a mushroom that has recently been shown to have antioxidant and anticancer activities. In this study, we first observed that hispolon exerted a dose-dependent inhibitory effect on invasion and motility, but not on adhesion, of the highly metastatic SK-Hep1 cells in the absence of cytotoxicity. Mechanistically, hispolon decreased the expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-plasminogen activator (uPA) in a concentration-dependent manner. Hispolon also inhibited phosphotylation of extracellular signaling-regulating kinase1/2 (ERK1/2), phosphatidylinositol-3-kinase/serine/threonine protein kinase (or protein kinase B (PI3K/Akt), and focal adhesion kinase (FAK). Furthermore, treatment of SK-Hep1 cells with an inhibitor specific for ERK1/2 (PD98256) decreased the expression of MMP-2, and MMP-9. These results demonstrate that hispolon can inhibit the metastasis of SK-Hep1 cells by reduced expression of MMP-2, MMP-9, and uPA through the suppression of the FAK signaling pathway and of the activity of PI3K/Akt and Ras homologue gene family, member A (RhoA). These findings suggest that hispolon may be used as an antimetastatic agent

Hepatoprotective Effect of Shidagonglao on Acute Liver Injury Induced by Carbon Tetrachloride

This study investigates the hepatoprotective activity of ethanol extract from Shidagonglao roots (SDGL(EtOH)). The hepatoprotective effect of SDGL(EtOH) (20, 100 and 500 mg/kg) was analyzed on carbon tetrachloride (CCl(4))-induced acute liver injury. Rats pretreated orally with SDGL(EtOH) (100 and 500 mg/kg) and silymarin (200 mg/kg) for 3 consecutive days prior to the administration of a single dose of 50% CCl(4) (0.10ml/100 g of bw, ip) significantly prevented the increases in the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in CCl(4)-treated rats. Histological analysis also showed that SDGL(EtOH) (100 and 500 mg/kg) and silymarin reduced the incidence of liver lesions including vacuole formation, neutrophil infiltration and necrosis of hepatocytes induced by CCl(4) in rats. Moreover, the SDGL(EtOH) (100 and 500 mg/kg) increased the activities of anti-oxidative enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRd) and decreased malondialdehyde (MDA) level in liver, as compared to those in the CCl(4)-treated group. Furthermore, SDGL(EtOH) (100 and 500 mg/kg) and silymarin attenuated the increased levels of tumor necrosis factor-alpha (TNF-alpha) in serum and nitric oxide (NO) in liver as compared to the CCl(4)-treated group. The hepatoprotective mechanisms of SDGL(EtOH) are likely related to inhibition of TNF-alpha, MDA and NO productions via increasing the activities of antioxidant enzymes (SOD, GPx and GRd). These experimental results suggest that SDGL(EtOH) can attenuate CCl(4)-induced acute liver injury in rats