title: Astragalus saponins modulate cell invasiveness and angiogenesis in human gastric adenocarcinoma cells.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: K K
authors.initials: KK
authors.lastname: Auyeung
authors.forename: P K
authors.initials: PK
authors.lastname: Woo
authors.forename: P C
authors.initials: PC
authors.lastname: Law
authors.forename: J K
authors.initials: JK
authors.lastname: Ko
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D042501:Angiogenic Proteins / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D027883:Astragalus Plant / Q000737:chemistry; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins; D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D010936:Plant Extracts; D012503:Saponins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9