Mithramycin Represses MDR1 Gene Expression in Vitro, Modulating Multidrug Resistance

Abstract

The effect of an aureolic acid, mithramycin (MTM) on multidrug resistance (MDR) was investigated. At a concentration of 0.02-0.1 mg/ml (about 20-90 μM), MTM repressed MDR1 gene transcription of SBC-3/ADM, a MDR-phenotype subline derived from human small cell lung tumor. Under the same conditions, another aureolic acid, chromomycin A₃, showed potent cytotoxicity. FACS analysis revealed that 5 μM MTM depleted the P-glycoprotein (Pgp) and lowered the efflux activity of SBC-3/ADM cells. Furthermore, MTM sensitized the cells against adriamycin^[○!R]. These results suggest that MTM would be a useful modulator of MDR induced by Pgp.