ADRIAMYCIN RESISTANCE MODULATION INDUCED BY LONIDAMINE IN HUMAN BREAST-CANCER CELLS

The effect of Lonidamine (LND), an energolytic chemosensitizing agent, on rite MDR (multidrug resistant) phenotype of a human breast cancer cell line (MCF-7) has been studied. The intracellular adriamycin (ADR) accumulation and distribution, the plasma membrane potential and the P170 glycoprotein phosphorylation, have been analysed after LND treatm ent. The analysis of the subcellular localisation of ADR in both wild type and resistant MCF-7 cells treated with ADR or ADR + LND, revealed that LND induced an ADR intracellular redistribution in both cell lin es. MCF-7 ADR resistant cells exposed to LND (50 mu g/ml) showed a cha nge in the electrical charges distribution across the plasma membrane and a time-dependent reduction of P170 phosphorylation (70 % at 24 hr) . These effects were associated with a marked increase in intracellula r ADR accumulation in resistant cells.