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 cytotoxicit...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 1997/12/15, Vol.20(12), pp.1303-1306
Main Authors: FURUSAWA, Shinobu, NAKANO, Shinya, WU, Jianghong, SASAKI, Ken-ichi, TAKAYANAGI, Motoaki, TAKAYANAGI, Yoshio
Format: Article
Language:English
Subjects:
Animals
Antibacterial agents
Antibiotics, Antineoplastic - pharmacology
Antibiotics, Antitubercular - pharmacology
Antibiotics. Antiinfectious agents. Antiparasitic agents
apoptosis
Apoptosis - drug effects
Biological and medical sciences
cell cycle
Cell Cycle - drug effects
cytotoxicity
Doxorubicin - analogs & derivatives
Doxorubicin - pharmacology
Drug Resistance, Multiple
Drug Synergism
Gene Expression Regulation, Neoplastic - drug effects
Genes, MDR - drug effects
Leukemia P388 - drug therapy
Leukemia P388 - metabolism
Medical sciences
Mice
multidrug-resistant cell
Pharmacology. Drug treatments
pirarubicin
rifampicin
Rifampin - pharmacology
Tetrazolium Salts
Thiazoles
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Summary: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.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.20.1303