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 microM), 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 microm MTM depleted the P-glycoprotein (Pgp) and lowered the efflux activity of SBC-3/ADM cells. Furthermore, MTM sensitized the cells against adriamycin. These results suggest that MTM would be a useful modulator of MDR induced by Pgp.
Tagashira
M
M
Foods and Pharmaceuticals Research and Development Laboratory, Asahi Breweries Ltd., Ibaraki, Japan. motoyuki.tagashira@asahibeer.co.jp
Kitagawa
T
T
Isonishi
S
S
Okamoto
A
A
Ochiai
K
K
Ohtake
Y
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D017931:DNA Primers; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008297:Male; D008926:Plicamycin / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D017931:DNA Primers; D004317:Doxorubicin; D008926:Plicamycin