Antileukemic effects of deferoxamine on human myeloid leukemia cell lines.
Deferoxamine (DFO) possesses antiproliferative activity against mitogen-stimulated lymphocytes, several tumor cell lines, and human leukemia and neuroblastoma cells. We have investigated its effects on the human myeloid leukemia lines HL-60, HEL, and U-937. In suspension culture, DFO causes a dose-dependent inhibition of proliferation of each cell line, with maximal inhibition observed at concentrations greater than 20 microM. These effects were prevented by cotreatment with iron salts and were at least partially reversible by removal of DFO from the culture system or addition of iron before 48 h of DFO exposure. Similar results were obtained in methylcellulose cultures of leukemic cells, with complete abolition of cell aggregates at day 7 in concentrations of 20 microM DFO or higher. DFO treatment caused a dose- and time-related decrease in DNA synthesis as measured by [3H]thymidine uptake, which was also reversed by treatment with iron salts. DFO caused slight reduction in RNA synthesis and did not affect protein synthesis. DFO caused significant antiproliferative effects on three myeloid leukemia cell lines, associated with inhibition of DNA synthesis, with in vitro effects observed at concentrations attainable in vivo. Evaluation of the antileukemic properties of DFO should continue.
Becton
D L
DL
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock.
Roberts
B
B
D000970:Antineoplastic Agents; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology*; D008747:Methylcellulose; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000187:drug effects; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D008747:Methylcellulose; D003676:Deferoxamine