Anti-metastatic potential of ethanol extract of Saussurea involucrata against hepatic cancer in vitro

Asian Pac J Cancer Prev. 2013;14(9):5397-402. doi: 10.7314/apjcp.2013.14.9.5397.

Abstract

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Blotting, Western
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / secondary*
  • Cell Adhesion / drug effects
  • Cell Aggregation / drug effects
  • Cell Cycle / drug effects
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Ethanol / chemistry*
  • Humans
  • In Vitro Techniques
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness
  • Phytotherapy*
  • Plant Extracts / pharmacology*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Saussurea / chemistry*
  • Tumor Cells, Cultured
  • Wound Healing / drug effects

Substances

  • Plant Extracts
  • RNA, Messenger
  • Ethanol
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9