Non-myelotoxic antitumour effects of L-dopa, buthionine sulphoximine and tamoxifen on neuroblastoma cells in vitro and in vivo.
The effects of three non-myelotoxic cancer drugs on the growth of neuroblastoma cells were investigated in vitro and in vivo: dihydroxyphenylalanine (L-dopa, a drug with selective toxicity for melanoma cells), DL-buthionine sulphoximine (BSO, a drug with radiosensitizing effects), and tamoxifen (a drug used in the treatment of human mammary carcinoma). In vivo these substances significantly reduced the weight of neuroblastoma tumour transplants in the mice (nude/nude) (P less than 0.05). A dose/effect relationship could be established. In vitro, the D50 was determined, using fibroblasts as controls. The growth of neuroblastoma tumours was inhibited by different mechanisms: L-dopa and its metabolite dopamine reduced the activity of tyrosinase, BSO reduced glutathione levels, and L-dopa and tamoxifen raised cAMP concentrations.
Busse
E
E
Abteilung für Hämatologie und Onkologie, Johann-Wolfgang-Goethe-Universität, Frankfurt/Main, Federal Republic of Germany.
Bartsch
O
O
Kornhuber
B
B
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019328:Buthionine Sulfoximine; D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D014442:Monophenol Monooxygenase / Q000187:drug effects / Q000378:metabolism; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D013629:Tamoxifen; D008717:Methionine Sulfoximine; D007980:Levodopa; D019328:Buthionine Sulfoximine; D000242:Cyclic AMP; D014442:Monophenol Monooxygenase; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D005978:Glutathione