Anti-metastatic Potential of Ethanol Extract of Saussurea involucrata against Hepatic Cancer in vitro

Abstract

The rates of morbidity and mortality of hepatocellular carcinoma (HCC) have not lessened because ofdifficulty in treating tumor metastasis. Mongolian Saussurea involucrata (SIE) possesses various anticanceractivities, including apoptosis and cell cycle arrest. However, detailed effects and molecular mechanisms of SIEon metastasis are unclear. Thus, the present study was undertaken to investigate antimetastatic effects on HCCcells as well as possible mechanisms. Effects of SIE on the growth, adhesion, migration, aggregation and invasionof the SK-Hep1 human HCC cell line were investigated. SIE inhibited cell growth of metastatic cells in dose- andtime-dependent manners. Incubation of SK-Hep1 cells with 200-400μg/mL of SIE significantly inhibited celladhesion to gelatin-coated substrate. In the migration (wound healing) and aggregation assays, SIE treated cellsshowed lower levels than untreated cells. Invasion assays revealed that SIE treatment inhibited cell invasioncapacity of HCC cells substantially. Quantitative real time PCR showed inhibitory effects of SIE on MMP-2/-9and MT1-MMP mRNA levels, and stimulatory effects on TIMP-1, an inhibitor of MMPs. The present study notonly demonstrated that invasion and motility of cancer cells were inhibited by SIE, but also indicated that sucheffects were likely associated with the decrease in MMP-2/-9 expression of SK-Hep1 cells. From these results, itwas suggested that SIE could be used as potential anti-tumor agent.