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Astragalus saponins modulate cell invasiveness and angiogenesis in human gastric adenocarcinoma cells
K K Auyeung1, P K Woo, P C Law
1Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
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.
Insights
Astragalus saponins (AST) show anti-cancer effects by inducing apoptosis and inhibiting growth in gastric cancer cells. AST also reduces cancer cell invasion and angiogenesis, suggesting potential as a chemotherapeutic agent.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Astragalus saponins (AST) previously demonstrated anti-tumorigenic effects on colon cancer cells.
- Gastric adenocarcinoma (AGS) cells are a relevant model for studying gastric cancer progression.
Purpose of the Study:
- To investigate the anti-angiogenic and anti-invasive properties of AST in human gastric adenocarcinoma cells (AGS).
- To elucidate the underlying molecular mechanisms of AST's effects on AGS cells.
Main Methods:
- Cell viability was assessed using MTT assay.
- Western blotting and PI staining were used to analyze protein expression and cell cycle progression.
- Matrigel invasion assays evaluated cell invasiveness and associated protein expression (VEGF, MMPs).
Main Results:
- AST induced apoptosis in AGS cells via caspase 3 activation and PARP cleavage.
- AST treatment resulted in G2/M cell cycle arrest, leading to significant growth inhibition.
- AST significantly reduced AGS cell invasion and downregulated VEGF, MMP-2, and MMP-9 expression.
Conclusions:
- AST exhibits pro-apoptotic, anti-proliferative, anti-invasive, and anti-angiogenic activities in gastric cancer cells.
- These findings support the potential development of AST as a chemotherapeutic agent for advanced and metastatic gastric cancers.
