[Augmentation of pirarubicin cytotoxicity by chlorpromazine in doxorubicin-resistant mouse P388 leukemia cells].
The intracellular uptake, retention and cytotoxicity of pirarubicin, an anthracycline derivative, combined with chlorpromazine were investigated in doxorubicin-resistant mouse P388 leukemia (P388/DXR) cells. The number of viable cells was determined by the dye exclusion method. Chlorpromazine increased the cytotoxicity of pirarubicin in a dose-related manner in P388/DXR cells. A similar dose-response relationship was observed for chlorpromazine in increasing net intracellular pirarubicin accumulation. The accumulation was based on block of enhanced pirarubicin efflux from resistant cells by chlorpromazine. However, chlorpromazine did not affect cytotoxicity or transport of pirarubicin in the drug-sensitive cell line. The possible mechanisms of the restoration of pirarubicin sensitivity in P388/DXR cells by chlorpromazine are discussed.
Shibata
H
H
Dept. Pharmacol. Toxicol., Tohoku College of Pharmacy, Sendai, Japan.
Sano
F
F
Furusawa
S
S
Kawauchi
H
H
Sasaki
K
K
Takayanagi
Y
Y
D000818:Animals; D000970:Antineoplastic Agents; D002746:Chlorpromazine / Q000494:pharmacology*; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D004351:Drug Resistance; D004357:Drug Synergism; D007941:Leukemia P388 / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004317:Doxorubicin; C027260:pirarubicin; D002746:Chlorpromazine