Potentiation of pirarubicin activity in multidrug resistant cells by rifampicin.
The effect of the anti-tuberculosis drug rifampicin on pirarubicin activity was investigated in multidrug-resistant cells overexpressing P-glycoprotein. Rifampicin increased the sensitivity of pirarubicin to anthracycline-resistant mouse leukemic P388 cells and significantly enhanced the cytotoxicity and intracellular accumulation of pirarubicin in resistant cells, but had no effect in parent cells. By contrast, two other rifamycins, rifamycin B and SV, had no effect on pirarubicin accumulation in resistant cells. Rifampicin also enhanced pirarubicin-induced apoptosis and G2/M blockade on the cell cycle in resistant cells. These results show that rifampicin enhances the cytotoxic action of pirarubicin in resistant cells, at least partly via the inhibition of cellular pirarubicin efflux.
Furusawa
S
S
Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku College of Pharmacy, Sendai, Japan.
Nakano
S
S
Wu
J
J
Sasaki
K
K
Takayanagi
M
M
Takayanagi
Y
Y
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019450:Genes, MDR / Q000187:drug effects; D007941:Leukemia P388 / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D012293:Rifampin / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles
D000903:Antibiotics, Antineoplastic; D000904:Antibiotics, Antitubercular; D013778:Tetrazolium Salts; D013844:Thiazoles; D004317:Doxorubicin; C027260:pirarubicin; C022616:thiazolyl blue; D012293:Rifampin