6-fluorodopamine selectively destroys neuroblastoma cells expressing the noradrenaline transporter.
BACKGROUND
6-Hydroxydopamine (6-OHDA) was used for ex vivo purging of bone marrow from neuroblastoma cells before autologous transplantation. However, this concept failed because of the rapid autoxidation of 6-OHDA, which leads to the generation of cytotoxic reactive oxygen species (ROS), mainly in the incubation medium before 6-OHDA can be incorporated by neuroblastoma cells.


METHODS
We based our experiments on the theory that, in contrast, 6-fluorodopamine (6-FDA), which is slowly converted to 6-OHDA at neutral pH, is able to enter neuroblastoma cells via the noradrenaline transporter (NA-T). Therefore, most ROS are generated inside the target cells.


RESULTS
Small amounts of ascorbate prevent the extracellular conversion of 6-FDA to 6-OHDA without affecting its cytotoxicity, leading to an even more selective effect of 6-FDA.


CONCLUSIONS
We conclude that 6-FDA is a promising substance for selective destruction of NA-T-positive neuroblastoma cells.
Seitz
G
G
Children's University Hospital, Tuebingen, Germany.
Bruchelt
G
G
Kuci
Z
Z
Roginsky
V A
VA
Wolburg
H
H
Stegmann
H B
HB
Niethammer
D
D
D001205:Ascorbic Acid / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics*; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D009638:Norepinephrine / Q000235:genetics*; D050484:Norepinephrine Plasma Membrane Transport Proteins; D016627:Oxidopamine / Q000494:pharmacology; D027981:Symporters; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; D027981:Symporters; C029253:6-fluorodopamine; D016627:Oxidopamine; D001205:Ascorbic Acid; D004298:Dopamine; D009638:Norepinephrine