Effect of desferrioxamine and hydroxypyridones on hemopoietic progenitors and neuroectodermal tumor cells.
The iron chelator desferrioxamine (DFO) has been shown to inhibit the proliferation of hemopoietic progenitors and several tumor cell lines. We have compared the in viro hemopoietic inhibitory effect of desferrioxamine (DFO) and hydroxypyridones (HPOs) on hemopoietic progenitors and two human neuroectodermal (NE) tumor cell lines, NB 100 and SKNMC. Both DFO and HPOs showed a direct dose-related inhibitory effect on BFU-E and CFU-GM obtained from purified human non-T MNAC (T-lymphocyte-depleted nonadherent mononuclear cells) and CD34+ cells. DFO and HPOs displayed both an inhibitory and a cytotoxic effect on NE cell lines. We calculated the ratio between NE cell and hemopoietic cell growth inhibition for a range of concentrations of chelators. DFO showed the most satisfactory ratio. This suggests that DFO is still the most preferable chelating agent for the treatment of neuroblastoma, since it combines the highest antineuroblastoma effect with the lowest hematopoietic toxicity.
Timeus
F
F
Department of Pediatric Hematology-Oncology, University of Turin, Italy.
Valle
P
P
Crescenzio
N
N
Ruggieri
L
L
Rosso
P
P
Pagliardi
G L
GL
Cordero di Montezemolo
L
L
Gabutti
V
V
Ramenghi
U
U
D013956:Antithyroid Agents / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D017599:Neuroectodermal Tumors / Q000473:pathology*; D011728:Pyridones / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured
D013956:Antithyroid Agents; D011728:Pyridones; D014316:Tritium; C020366:3-hydroxy-4-pyridone; D003676:Deferoxamine; D013936:Thymidine