Cytotoxic effects of 6-hydroxydopamine, merocyanine-540 and related compounds on human neuroblastoma and hematopoietic stem cells.
6-Hydroxydopamine(6-OHDA) and Merocyanine-540(MC-540) have been used clinically for purging of neuroblastoma cells prior to autologous bone marrow transplantation. Both substances were found to be more toxic against neuroblastoma cells than against hematopoietic stem cells. The more pronounced cytotoxic effects of 6-OHDA against neuroblastoma cells were not caused by its selective uptake; the rapid autooxidation at physiological pH leads to the formation of H2O2 already in the incubation medium. Cytotoxic effects were not detected in short-time test systems (4 hour chromium-51 release assay) but only after longer incubation periods. In contrast, MC-540 proved to be toxic almost equally in short- and long-time test systems. 4-Hydroxynonenal(4-HNE) that may be formed in the plasma membrane subsequently to photoactivation of MC-540 was only slightly more toxic to neuroblastoma cells than to hematopoietic cells. Although the use of 6-OHDA and MC-540 in bone marrow purging has some limitations, the sensitivity of neuroblastoma cells against reactive oxygen compounds may be exploited more generally for therapy of this tumor.
Bruchelt
G
G
Children's Hospital, Dept. Hematology and Oncology, University of Tuebingen, FRG.
Grygar
G
G
Treuner
J
J
Esterbauer
H
H
Niethammer
D
D
D000447:Aldehydes / Q000494:pharmacology; D000970:Antineoplastic Agents; D002470:Cell Survival / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology* / Q000633:toxicity; D009447:Neuroblastoma / Q000188:drug therapy*; D016627:Oxidopamine; D011744:Pyrimidinones / Q000494:pharmacology* / Q000633:toxicity; D014407:Tumor Cells, Cultured
D000447:Aldehydes; D000970:Antineoplastic Agents; D006892:Hydroxydopamines; D011744:Pyrimidinones; C003954:merocyanine dye; D016627:Oxidopamine; D006861:Hydrogen Peroxide; C027576:4-hydroxy-2-nonenal