Quinine circumvents the doxorubicin resistance of a multidrug resistant human leukemic cell-line, K562/DXR.
Reversal of multidrug resistance (MDR) has been obtained in vitro by a variety of agents but clinical use of these resistance modifiers is hampered by their own toxicity. Quinine, the natural isomer of quinidine, is demonstrated to circumvent doxorubicin (DXR) resistance of an MDR human leukemic cell-line, K562/DXR. In culture medium, quinine (5 mu/ml or more) significantly increases cytotoxicity and accumulation of DXR in the resistant cells but not in the parental sensitive cells. When quinine is administered by continuous intravenous infusion in the doses conventionally used in chloroquino-resistant malaria (30 mg/kg/d), serum levels reach 8-11 micrograms/ml without prohibitive toxicity. Sera from quinine-treated patients enhance DXR uptake in K562/DXR cells in dose-dependent fashion. The conditions for the safe use of quinine as an MDR modifier in the treatment of refractory human hemopoietic malignancies are defined.
Solary
E
E
Hématologie Clinique, Centre Hospitalier Universitaire Le Bocage, Dijon, France.
Velay
I
I
Chauffert
B
B
Caillot
D
D
Bidan
J M
JM
Dumas
M
M
Casasnovas
O
O
Guy
H
H
D004317:Doxorubicin / Q000378:metabolism / Q000627:therapeutic use*; D004351:Drug Resistance / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D011803:Quinine / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D004317:Doxorubicin; D011803:Quinine