Astragalus saponins modulate cell invasiveness and angiogenesis in human gastric adenocarcinoma cells

J Ethnopharmacol. 2012 Jun 1;141(2):635-41. doi: 10.1016/j.jep.2011.08.010. Epub 2011 Aug 12.


Aim of the study: We had reported that Astragalus saponins (AST) exert promising anti-tumorigenic effects by suppressing the growth of HT-29 human colon cancer cells and tumor xenograft. In the present study, we further investigated the anti-angiogenic property of AST in human gastric adenocarcinoma cells (AGS) and attempted to elucidate the underlying mechanism.

Materials and methods: Viability of AGS cells was measured by using the MTT reduction method. Western blotting was performed to examine the effect of AST on apoptotic- and cell growth-related protein expression. Effect of AST on cell cycle progression was also evaluated using PI staining. A Matrigel invasion assay was then employed to demonstrate the effect of AST on the invasiveness of gastric cancer cells. The expression of invasion-associated proteins (VEGF and MMPs) was also investigated.

Results: AST could induce apoptosis in AGS cells by activating caspase 3 with subsequent cleavage of poly(ADP-ribose) polymerase. Besides, cell cycle arrest at the G2/M phase had been observed in AST-treated cells, leading to substantial growth inhibition. The anti-proliferative effect of AST was associated with the regulation of cyclin B1, p21 and c-myc. Results indicate that the number of AGS cells invaded through the Matrigel membrane was significantly reduced upon AST treatment, with concomitant down-regulation of the pro-angiogenic protein vascular endothelial growth factor (VEGF) as well as the metastatic proteins metalloproteinase (MMP)-2 and MMP-9.

Conclusion: AST derived from the medicinal plant Astragalus membranaceus could modulate the invasiveness and angiogenesis of AGS cells besides its pro-apoptotic and anti-proliferative activities. These findings also suggest that AST has the potential to be further developed into an effective chemotherapeutic agent in treating advanced and metastatic gastric cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood supply
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Angiogenesis Inhibitors / isolation & purification
  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenic Proteins / metabolism
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Astragalus Plant* / chemistry
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / prevention & control*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Saponins / isolation & purification
  • Saponins / pharmacology*
  • Stomach Neoplasms / blood supply
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Time Factors
  • Vascular Endothelial Growth Factor A / metabolism


  • Angiogenesis Inhibitors
  • Angiogenic Proteins
  • Antineoplastic Agents, Phytogenic
  • Apoptosis Regulatory Proteins
  • Cell Cycle Proteins
  • Plant Extracts
  • Saponins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9