Deferoxamine inhibition of human neuroblastoma viability and proliferation.
Patients with widespread neuroblastoma (NB) frequently have elevated serum ferritin levels, and recently anti-NB effects of the iron chelator deferoxamine (DFO) have been reported. We have investigated the effect of DFO on human bone marrow NB cells from two untreated children with Evans Stage IV disease. DFO treatment caused dose- and time-dependent cytotoxicity of NB cells, with maximal killing at exposure to 50 micron DFO for 72 h. Cytotoxicity was prevented by cotreatment with stoichiometric amounts of iron salts and reversible by removal of DFO or addition of iron salts within 48 h of treatment. Additionally, DFO inhibited clonal growth of human bone marrow NB cells in methylcellulose in a time- and dose-dependent manner. These effects were also prevented by cotreatment with iron salts. Thus, DFO has potent antitumor effects on human NB cells which appear to be related to iron deprivation. DFO should be considered for further preclinical evaluation as an anti-NB agent.
Becton
D L
DL
University of Arkansas for Medical Sciences, Little Rock.
Bryles
P
P
D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005293:Ferritins / Q000097:blood; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy*; D013997:Time Factors
D005293:Ferritins; D003676:Deferoxamine