Mithramycin represses MDR1 gene expression in vitro, modulating multidrug resistance

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 mu M), MTM repressed MDR1 gene transcription of SBC-3/ADM, a MDR-phenotype su bline derived from human small cell lung tumor, Under the same conditions, another aureolic acid, chromomycin A(3), showed potent cytotoxicity. FAGS a nalysis revealed that 5 mu M MTM depleted the P-glycoprotein (Pgp) and lowe red the efflux activity of SBC-3/ADM cells, Furthermore, MTM sensitized the cells against adriamycin(R). These results suggest that MTM would he a use ful modulator of MDR induced by Pgp.