Synergistic antiproliferative effects on HL-60 cells: deferoxamine enhances cytosine arabinoside, methotrexate, and daunorubicin cytotoxicity.
Deferoxamine (DFO), a widely used therapeutic iron chelator, was found to inhibit proliferation of the promyelocytic leukemia cell line HL-60 in a dose-dependent fashion when tested in a clonogenic assay at concentrations ranging from 1.0 to 10.0 microM. Cytosine arabinoside, methotrexate, and daunorubicin also produced dose-dependent inhibition of HL-60 colony growth when tested singly in vitro. When DFO, 1.0 microM, was included with each agent in dose-response studies, a synergistic enhancement of the antiproliferative effects was observed. This synergism probably results from a DFO-induced decrease in intracellular levels of deoxyribonucleoside triphosphates and an inhibition of the cells at the early S-phase of cell cycle. Our data suggest that DFO has potential as an adjunctive antileukemic agent.
Estrov
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Division of Hematology, Hospital for Sick Children, Toronto, Canada.
Cohen
A
A
Gelfand
E W
EW
Freedman
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MH
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002460:Cell Line; D003561:Cytarabine / Q000494:pharmacology*; D003630:Daunorubicin / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D008727:Methotrexate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D003676:Deferoxamine; D008727:Methotrexate; D003630:Daunorubicin