Ardipusilloside inhibits survival, invasion and metastasis of human hepatocellular carcinoma cells

Phytomedicine. 2012 May 15;19(7):603-8. doi: 10.1016/j.phymed.2012.01.003. Epub 2012 Feb 18.

Abstract

Ethnopharmacological relevance: Ardipusilloside I is a triterpene-saponin isolated from the Traditional Chinese Medicine Ardisia pusilla A. DC. Its effects and mechanism on invasion and metastasis of liver cancer cells are unclear.

Materials and methods: The human hepatocellular carcinoma cell line HepG2 and SMMC-7721 cells were treated with different doses of Ardipusilloside I. Cellular survival, in vitro migration and invasion were evaluated. In vivo metastatic abilities of the HCC cells were detected. We further investigated expression and phosphorylation of Mek, Erk and Akt by using Western blot. MMP2 and MMP9 activities were evaluated by gelatin zymography. E-cadherin expression, Rac1 and Cdc42 activities were examined by Western blot and pull-down assay.

Results: Ardipusilloside I inhibited invasion and metastasis of HCC cells both in vitro and in vivo by reducing the protein expressions of metalloproteinase (MMP)-9 and MMP2 proteins. Ardipusilloside I activated Rac1 that enhanced E-cadherin activity and resulted in significantly less metastasis.

Conclusion: Our findings indicate that Ardipusilloside I has the potential of inhibition of liver cancer survival, invasion and metastasis both in vitro and in vivo.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Ardisia / chemistry*
  • Blotting, Western
  • Cadherins / metabolism
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Collagenases / metabolism*
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / pharmacology
  • Oleanolic Acid / therapeutic use
  • Phytotherapy*
  • Protein-Serine-Threonine Kinases / metabolism
  • Saponins / pharmacology
  • Saponins / therapeutic use*
  • cdc42 GTP-Binding Protein / metabolism
  • rac1 GTP-Binding Protein / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Cadherins
  • Drugs, Chinese Herbal
  • Saponins
  • ardipusilloside I
  • Oleanolic Acid
  • Protein-Serine-Threonine Kinases
  • Collagenases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • cdc42 GTP-Binding Protein
  • rac1 GTP-Binding Protein