Synergistic antiproliferative effects on HL-60 cells: deferoxamine enhances cytosine arabinoside, methotrexate, and daunorubicin cytotoxicity

Am J Pediatr Hematol Oncol. Winter 1988;10(4):288-91. doi: 10.1097/00043426-198824000-00003.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology*
  • Cell Line
  • Cytarabine / pharmacology*
  • Daunorubicin / pharmacology*
  • Deferoxamine / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Humans
  • Leukemia, Promyelocytic, Acute / pathology*
  • Methotrexate / pharmacology*
  • Tumor Cells, Cultured / drug effects

Substances

  • Antimetabolites, Antineoplastic
  • Cytarabine
  • Deferoxamine
  • Methotrexate
  • Daunorubicin