Table of Contents
Metal-Based Drugs
Volume 1, Issue 2-3, Pages 175-182

Analysis of Multidrug Transporter in Living Cells. Inhibition of P-glycoprotein-mediated Efflux of Anthracyclines by Ionophores

Laboratoire de Chimie Bioinorganique, LPCB (URA CNRS 198), Université de Paris Nord, 74 rue Marcel Cachin, Bobigny F- 93012, France

Received 7 September 1993

Copyright © 1994 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


One of the major obstacles of chemotherapy is that, after repeated treatments, cellular resistance to the drug appears. The problem is that the tumor cells become resistant not only to the drugs which have been used during the treatment but also to other drugs which are structurally and functionally unrelated. This is termed ‘multidrug resistance’ (MDR). MDR is frequently associated with decreased drug accumulation resulting from enhanced drug efflux. This is correlated with the presence of a membrane protein, P-glycoprotein, which pumps a wide variety of drugs out of cells thus reducing their toxicity. The search for molecules able to reverse MDR is very important. We here report that mobile ionophores such as valinomycin, nonactin, nigericin, monensin, calcimycin, lasalocid inhibit the efflux of anthracycline by P-glycoprotein whereas, channel-forming ionophores such as gramicidin do not. Cyclosporin which is also a strong Ca2+ chelating agent also inhibits the P-glycoprotein-mediated efflux of anthracycline.