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

International Journal of Molecular Sciences
Helen M PalethorpeJennifer E Hardingham

Abstract

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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Citations

Aug 4, 2019·Pharmaceuticals·Maryam NakhjavaniJennifer E Hardingham
Oct 3, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Helen M PalethorpeJennifer E Hardingham
Jul 10, 2020·Journal of Natural Medicines·Li-Hua MuCan Yan
Oct 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maryam NakhjavaniJennifer E Hardingham
Nov 6, 2020·Nutrition and Cancer·Sudeepa GhoshAvik Acharya Chowdhury
Mar 2, 2021·Frontiers in Cell and Developmental Biology·Zihe HuoStephanie J Gros

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Methods Mentioned

BETA
electrophoresis
Assay
FCS

Software Mentioned

Image Lab
FlowJo

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