title: Importance of the difference in surface pressures of the cell membrane in doxorubicin resistant cells that do not express Pgp and ABCG2.
abstract: P-glycoprotein (Pgp) represents the archetypal mechanism of drug resistance. But Pgp alone cannot expel drugs. A small but growing body of works has demonstrated that the membrane biophysical properties are central to Pgp-mediated drug resistance. For example, a change in the membrane surface pressure is expected to support drug-Pgp interaction. An interesting aspect from these models is that under specific conditions, the membrane is predicted to take over Pgp concerning the mechanism of drug resistance especially when the surface pressure is high enough, at which point drugs remain physically blocked at the membrane level. However it remains to be determined experimentally whether the membrane itself could, on its own, affect drug entry into cells that have been selected by a low concentration of drug and that do not express transporters. We demonstrate here that in the case of the drug doxorubicin, alteration of the surface pressure of membrane leaflets drive drug resistance.
authors: University of Birmingham, School of Medicine and Dentistry, Edgbaston, Birmingham, UK.
authors: Charlotte
authors: C
authors: Bell
authors: Claire
authors: C
authors: Hill
authors: Christopher
authors: C
authors: Burton
authors: Adam
authors: A
authors: Blanchard
authors: Freya
authors: F
authors: Shephard
authors: Cyril
authors: C
authors: Rauch
mesh_terms: D000327:Adsorption; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism*; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020014:K562 Cells; D007700:Kinetics; D009068:Movement; D011312:Pressure; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin