Effects of verapamil on uptake and in vitro toxicity of anthracyclines in human leukemic blast cells.
The effect of a calcium channel blocker, verapamil, on intracellular uptake and cytotoxicity of anthracyclines in vitro was studied on leukemic cells from 32 patients with acute non-lymphoblastic leukemia. Cells were isolated from peripheral blood or bone-marrow and incubated with a concentration of 0.2 mumol/l, 0.5 mumol/l and/or 1.0 mumol/l of doxorubicin or daunorubicin in the absence and presence of verapamil at a concentration of 2 mumol/l and/or 10 mumol/l. Intracellular uptake was determined at the end of the incubations by photofluorometer and the in vitro cytotoxicity was determined after 5 days culturing in liquid medium by dye exclusion according to Weisenthal. Verapamil significantly increased the intracellular uptake of anthracyclines 0.5 mumol/l and 1.0 mumol/l and the cytotoxic effect of anthracyclines 0.2 mumol/l and 0.5 mumol/l and affected doxorubicin and daunorubicin equally. There were no significant differences between the two concentrations of verapamil. Cells from different FAB-groups were equally affected by verapamil. The effect on intracellular uptake was higher in cells from patients who were resistant to therapy compared to those who achieved a complete remission. We conclude that verapamil has an effect on intracellular uptake and cytotoxicity of anthracyclines on tumor cells from patients with acute non-lymphoblastic leukemia. The prognostic and therapeutic relevance of this has to be further evaluated.
Tidefelt
U
U
Department of Medicine, Huddinge Hospital, Sweden.
Sundman-Engberg
B
B
Paul
C
C
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic; D001826:Body Fluids / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism*; D003630:Daunorubicin / Q000633:toxicity; D004317:Doxorubicin / Q000633:toxicity; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism*; D007938:Leukemia / Q000097:blood* / Q000145:classification / Q000188:drug therapy; D008875:Middle Aged; D009279:Naphthacenes / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D012074:Remission Induction; D014700:Verapamil / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; D004317:Doxorubicin; D014700:Verapamil; D003630:Daunorubicin