Potentiation of pirarubicin cytotoxicity by dipyridamole in doxorubicin-resistant mouse P388 leukemia cells.
The activity of dipyridamole and its possible mechanisms which reverse the resistance of pirarubicin were studied in a P388 mouse leukemia cell lines. Dipyridamole alone was minimally cytotoxic in both of the doxorubicin-resistant cell line (P388/DOX) and the sensitive parent cell line (P388/S), but reversed pirarubicin-resistance in a dose-related manner in P388/DOX cells. A similar dose-response relationship was observed for dipyridamole by increasing net intracellular pirarubicin accumulation. The increase was a result of secondary blocking of enhanced pirarubicin efflux from P388/DOX cells. In contrast, dipyridamole did not affect cytotoxicity and transport in the drug-sensitive cell line. It is suggested that dipyridamole is a useful drug for modulation of the multidrug-resistance of cells.
Furusawa
S
S
Department of Pharmacology and Toxicology, Tohoku College of Pharmacy, Sendai, Japan.
Fujimura
T
T
Kawauchi
H
H
Sasaki
K
K
Takayanagi
Y
Y
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004176:Dipyridamole / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004351:Drug Resistance; D004357:Drug Synergism; D007941:Leukemia P388 / Q000188:drug therapy / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D004176:Dipyridamole; D004317:Doxorubicin; C027260:pirarubicin