Abstract
P-glycoprotein is capable of effluxing a broad range of cytosolic and membrane penetrating xenobiotic substrates, thus leading to multi-drug resistance and posing a threat for the therapeutic treatment of several diseases, including cancer and central nervous disorders. Herein, a virtual screening campaign followed by experimental validation in Caco-2, MDKCII, and MDKCII mdr1 transfected cell lines has been conducted for the identification of novel phospholipids with P-gp transportation inhibitory activity. Phosphatidylinositol-(1,2-dioctanoyl)-sodium salt (8∶0 PI) was found to significantly inhibit transmembrane P-gp transportation in vitro in a reproducible-, cell line-, and substrate-independent manner. Further tests are needed to determine whether this and other phosphatidylinositols could be co-administered with oral drugs to successfully increase their bioavailability. Moreover, as phosphatidylinositols and phosphoinositides are present in the human diet and are known to play an important role in signal transduction and cell motility, our finding could be of substantial interest for nutrition science as well.
| Original language | English |
|---|---|
| Article number | e60679 |
| Number of pages | 8 |
| Journal | PLoS ONE |
| Volume | 8 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 9 Apr 2013 |
Keywords
- Biological transport
- Caco-2 cells
- Cell line
- Chemistry, Pharmaceutical
- Cryoelectron microscopy
- Digoxin
- Drug discovery
- Drug resistance, Multiple
- Fluoresceins
- Humans
- Molecular docking simulation
- P-Glycoproteins
- Permeability
- Phosphatidylinositols
- Phospholipids
- Protein binding
- Protein conformation
- Journal article
- Research support, Non-U.S. Gov't
Access to Document
- Publisher final version
© 2013 Lucas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.