Effect of different exposures to desferrioxamine on neuroblastoma cell lines.
Desferrioxamine (DFO) has shown anti-proliferative and cytotoxic effects on several tumor cells. DFO is used at present in the treatment of neuroblastoma in combination with chemotherapy (D-CECaT regimen: cyclophosphamide, etoposide, carboplatin, and thiotepa). We compared the effect of continuous or intermittent exposures to DFO on 3H-thymidine uptake, viability, and cell cycle of human neuroblastoma (NB) cell lines. Our results show that continuous exposures to DFO cause dose- and time-dependent cytotoxicity of NB cells, while intermittent exposures result in significant NB cell toxicity only when using high DFO concentrations. By 3H-thymidine uptake, a significant inhibition of proliferation was observed only in continuous exposures. In addition, a consistent arrest in G1 phase was detected only in cultures treated continuously with high DFO concentrations. Our data indicate that 3H-thymidine uptake, viability, and cell cycle changes are proportional to the extent of exposure and concentration of DFO, suggesting that in vivo DFO continuous infusion may improve anti-neuroblastoma activity.
Valle
P
P
Pediatric Department, University of Torino, Italy.
Timeus
F
F
Piglione
M
M
Rosso
P
P
di Montezemolo
L C
LC
Crescenzio
N
N
Marranca
D
D
Ramenghi
U
U
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003676:Deferoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003676:Deferoxamine; D013936:Thymidine