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.