Comparison of activity of deferoxamine with that of oral iron chelators against human neuroblastoma cell lines.
The iron chelator, deferoxamine, has demonstrated cytotoxicity against neuroblastoma cells. In this study we examined the in vitro antineuroblastoma activity of several potentially less expensive oral chelating agents. On a mole for mole basis, 1-hydroxypyridine-2-thionine (omadine) had 100 times the cytotoxicity of deferoxamine. 1,2-Dimethyl-3-hydroxypyrid-4-one also caused demonstrable cell death but at considerably higher molar concentrations than those required for deferoxamine. 2,3-Dihydroxybenzoic acid had no effect on neuroblastoma cell viability over a range of concentrations. In contrast to the effect of both deferoxamine and 1,2-Dimethyl-3-hydroxypyrid-4-one, those due to omadine were permanent within 24 hours of incubation, were not significantly altered by the presence of ionic iron, and correlated with an increase in the percentage of cells in the S-G2-M phases of the cell cycle. On the basis of these in vitro studies, we believe that the use of omadine in particular and iron chelators in general, by themselves or as cell cycle-recruiting agents together with standard cell cycle specific drugs, is an approach to the treatment of cancer worth further investigation.
Blatt
J
J
Department of Pediatrics, Children's Hospital, Pittsburgh, Pennsylvania 15213.
Taylor
S R
SR
Kontoghiorghes
G J
GJ
D000284:Administration, Oral; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000077543:Deferiprone; D003676:Deferoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology*; D009447:Neuroblastoma / Q000188:drug therapy*; D011725:Pyridines / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D013871:Thiones; D014407:Tumor Cells, Cultured / Q000187:drug effects
D062385:Hydroxybenzoates; D011725:Pyridines; D011728:Pyridones; D013871:Thiones; D000077543:Deferiprone; C008704:pyrithione; C009135:2,3-dihydroxybenzoic acid; D003676:Deferoxamine