Background: Angiogenesis is an important process in cancer progression and involves the recruitment of endothelial cells. Expression of aquaporin-1 (AQP1) in endothelial cells facilitates their migration and angiogenesis in cancer. We tested the AQP1 inhibitor bacopaside II [1], derived from the medicinal herb Bacopa monnieri, on endothelial cell migration, tube formation, and viability in vitro.
Method: The expression of AQP1 was confirmed in mouse endothelial cell lines (2H11 and 3B11) and human umbilical vein endothelial cells (HUVEC). The effects of bacopaside II on endothelial cell migration, angiogenesis, viability and apoptosis were assessed by wound closure, endothelial tube formation, MTS and annexin-V/propidium iodide assays respectively. Results were compared relative to vehicle controls and statistical significance was determined by one-way ANOVA.
Results: Bacopaside II significantly reduced migration of 2H11 at 15 μM (p < 0.0001), and of 3B11 at 12.5 μM (p < 0.0001) with complete inhibition at 15 μM (p < 0.0001). HUVECs were most sensitive with a significant reduction occurring at 10 μM (p < 0.0001). Tube formation was reduced with 15 μM bacopaside II for each cell line and also with 10 μM for 3B11 (p < 0.0001). Cell viability was significantly reduced for 2H11 at 15 μM (p = 0.030), and for 3B11 at 12.5 μM (p = 0.014) and 15 μM (p = 0.0001). There was an increase in the percentage of apoptotic cells at 12.5 μM and 15 μM for the three cell lines.
Conclusion: This is the first report of AQP1 inhibitor, bacopaside II, reducing endothelial cell migration and angiogenesis and increasing apoptosis in vitro. These results suggest bacopaside II as a potential anti-angiogenic therapy to slow cancer progression, providing the rationale for investigating its effects in vivo.