6-fluorodopamine selectively destroys neuroblastoma cells expressing the noradrenaline transporter.

Abstract

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.

• Authors: G Seitz, G Bruchelt, Z Kuci, V A Roginsky, H Wolburg, H B Stegmann, D Niethammer
• Journal: Medical and pediatric oncology (Med Pediatr Oncol) Vol. 35 Issue 6 Pg. 612-5 (Dec 2000) ISSN: 0098-1532 [Print] United States
• PMID: 11107129 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2000 Wiley-Liss, Inc.

Chemical References

• Carrier Proteins
• Norepinephrine Plasma Membrane Transport Proteins
• SLC6A2 protein, human
• Symporters
• 6-fluorodopamine
• Oxidopamine
• Ascorbic Acid
• Dopamine
• Norepinephrine

Topics

• Ascorbic Acid (pharmacology)
• Carrier Proteins (genetics)
• Dopamine (analogs & derivatives, pharmacology)
• Gene Expression Regulation, Neoplastic
• Humans
• Neuroblastoma (genetics, pathology)
• Norepinephrine (genetics)
• Norepinephrine Plasma Membrane Transport Proteins
• Oxidopamine (pharmacology)
• Symporters
• Tumor Cells, Cultured