6-fluorodopamine selectively destroys neuroblastoma cells expressing the noradrenaline transporter

• Published in: Medical and pediatric oncology 2000-12, Vol.35 (6), p.612-615
• Main Authors: Seitz, Gabriele, Bruchelt, Gernot, Kuci, Zyrafete, Roginsky, Vitaly A., Wolburg, Hartwig, Stegmann, Hartmut B., Niethammer, Dietrich
• Format: Article
• Language: English
• Subjects: 6-FDA; Ascorbic Acid - pharmacology; Carrier Proteins - genetics; Dopamine - analogs & derivatives; Dopamine - pharmacology; Gene Expression Regulation, Neoplastic; Humans; neuroblastoma; Neuroblastoma - genetics; Neuroblastoma - pathology; noradrenaline transporter; Norepinephrine - genetics; Norepinephrine Plasma Membrane Transport Proteins; Oxidopamine - pharmacology; Symporters; Tumor Cells, Cultured
• ISSN: 0098-1532; 1096-911X
• DOI: 10.1002/1096-911X(20001201)35:6<612::AID-MPO26>3.0.CO;2-U

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. Procedure 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. Med. Pediatr. Oncol. 35:612–615, 2000. © 2000 Wiley‐Liss, Inc.