http://dx.doi.org/10.1016/j.jep.2011.08.010">
 

Document Type

Journal Article

Department/Unit

School of Chinese Medicine

Title

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

Language

English

Abstract

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. © 2011 Elsevier Ireland Ltd. All rights reserved.

Keywords

AGS cells, Angiogenesis, AST, Cell invasiveness, Cell proliferation

Publication Date

2012

Source Publication Title

Journal of Ethnopharmacology

Volume

141

Issue

2

Start Page

635

End Page

641

Publisher

Elsevier

ISSN (print)

03788741

ISSN (electronic)

18727573

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