Abstract
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