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Type: Journal article
Title: Differential inhibition of water and ion channel activities of mammalian aquaporin-1 by two structurally related bacopaside compounds derived from the medicinal plant bacopa monnieri
Author: Pei, J.
Kourghi, M.
De Ieso, M.
Campbell, E.
Dorward, H.
Hardingham, J.
Yool, A.
Citation: Molecular Pharmacology, 2016; 90(4):496-507
Publisher: American Society for Pharmacology and Experimental Therapeutics
Issue Date: 2016
ISSN: 0026-895X
Statement of
Jinxin V. Pei, Mohamad Kourghi, Michael L. De Ieso, Ewan M. Campbell, Hilary S. Dorward, Jennifer E. Hardingham and Andrea J. Yool
Abstract: Aquaporin-1 (AQP1) is a major intrinsic protein that facilitates flux of water and other small solutes across cell membranes. In addition to its function as a water channel in maintaining fluid homeostasis, AQP1 also acts as a nonselective cation channel gated by cGMP, a property shown previously to facilitate rapid cell migration in a AQP1-expressing colon cancer cell line. Here we report two new modulators of AQP1 channels, bacopaside I and bacopaside II, isolated from the medicinal plant Bacopa monnieri Screening was conducted in the Xenopus oocyte expression system, using quantitative swelling and two-electrode voltage clamp techniques. Results showed bacopaside I blocked both the water (IC50 117 μM) and ion channel activities of AQP1 but did not alter AQP4 activity, whereas bacopaside II selectively blocked the AQP1 water channel (IC50 18 μM) without impairing the ionic conductance. These results fit with predictions from in silico molecular modeling. Both bacopasides were tested in migration assays using HT29 and SW480 colon cancer cell lines, with high and low levels of AQP1 expression, respectively. Bacopaside I (IC50 48 μM) and bacopaside II (IC50 14 μM) impaired migration of HT29 cells but had minimal effect on SW480 cell migration. Our results are the first to identify differential AQP1 modulators isolated from a medicinal plant. Bacopasides could serve as novel lead compounds for pharmaceutic development of selective aquaporin modulators.
Keywords: Cell Line, Tumor
Xenopus laevis
Plants, Medicinal
Ion Channels
Cyclic GMP
Plant Extracts
Cell Death
Cell Movement
Cell Survival
Ion Channel Gating
Binding Sites
Time Factors
Aquaporin 1
Time-Lapse Imaging
Molecular Docking Simulation
Rights: Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics
DOI: 10.1124/mol.116.105882
Grant ID:
Appears in Collections:Aurora harvest 7
Medicine publications

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