6-fluorodopamine selectively destroys neuroblastoma cells expressing the noradrenaline transporter
| Autor: | Hartmut B. Stegmann, Vitaly A. Roginsky, Gabriele Seitz, Dietrich Niethammer, Zyrafete Kuçi, Gernot Bruchelt, Hartwig Wolburg |
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| Rok vydání: | 2000 |
| Předmět: |
Cancer Research
animal structures Dopamine Ascorbic Acid Biology Neuroblastoma Norepinephrine Tumor Cells Cultured Extracellular medicine Humans Autologous transplantation Cytotoxic T cell Oxidopamine Cytotoxicity chemistry.chemical_classification Reactive oxygen species Norepinephrine Plasma Membrane Transport Proteins Symporters medicine.disease Cell biology Gene Expression Regulation Neoplastic medicine.anatomical_structure nervous system Oncology Biochemistry chemistry Pediatrics Perinatology and Child Health Bone marrow Carrier Proteins Ex vivo |
| Zdroj: | Medical and Pediatric Oncology. 35:612-615 |
| ISSN: | 1096-911X 0098-1532 |
| DOI: | 10.1002/1096-911x(20001201)35:6<612::aid-mpo26>3.0.co;2-u |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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