The Aquaporin 1 Inhibitor Bacopaside II Reduces Endothelial Cell Migration and Tubulogenesis and Induces Apoptosis

Helen M Palethorpe, Yoko Tomita, Eric Smith, Jinxin V Pei, Amanda R Townsend, Timothy J Price, Joanne P Young, Andrea J Yool, Jennifer E Hardingham
International Journal of Molecular Sciences 2018 February 26, 19 (3)
Expression of aquaporin-1 (AQP1) in endothelial cells is critical for their migration and angiogenesis in cancer. We tested the AQP1 inhibitor, bacopaside II, derived from medicinal plant Bacopa monnieri , on endothelial cell migration and tube-formation in vitro using mouse endothelial cell lines (2H11 and 3B11) and human umbilical vein endothelial cells (HUVEC). The effect of bacopaside II on viability, apoptosis, migration and tubulogenesis was assessed by a proliferation assay, annexin-V/propidium iodide flow cytometry, the scratch wound assay and endothelial tube-formation, respectively. Cell viability was reduced significantly for 2H11 at 15 μM ( p = 0.037), 3B11 at 12.5 μM ( p = 0.017) and HUVEC at 10 μM ( p < 0.0001). At 15 μM, the reduced viability was accompanied by an increase in apoptosis of 38%, 50% and 32% for 2H11, 3B11 and HUVEC, respectively. Bacopaside II at ≥10 μM significantly reduced migration of 2H11 ( p = 0.0002) and 3B11 ( p = 0.034). HUVECs were most sensitive with a significant reduction at ≥7.5 μM ( p = 0.037). Tube-formation was reduced with a 15 μM dose for all cell lines and 10 μM for 3B11 ( p < 0.0001). These results suggest that bacopaside II is a potential anti-angiogenic agent.

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