Uptake and cytotoxicity of ascorbic acid and dehydroascorbic acid in neuroblastoma (SK-N-SH) and neuroectodermal (SK-N-LO) cells. 1994

S L Baader, and G Bruchelt, and M C Trautner, and H Boschert, and D Niethammer
Children's Hospital, Department of Hematology and Oncology, University of Tuebingen, Germany.

Ascorbic acid (AA) was found to be cytotoxic to neuroblastoma cells in vitro and in vivo. In the present, study we investigated whether the reduced--(AA) or oxidized form (dehydroascorbic acid, DhAA) and its rapidly formed metabolites were the main cytotoxic agents. In neuroblastoma SK-N-SH cells, AA was found to be more cytotoxic than DhAA, although considerably higher amounts of [14C]DhAA than of [14C]AA were incorporated. In contrast, SK-N-LO cells derived from neuroectodermal tissue in fact showed a similar uptake but were much less injured by both substances. We observed that uptake of [14C]AA and [14C]DhAA was impaired in the presence of dithiothreitol and glutathione. Once inside the cell, [14C]DhAA was partially reduced to [14C]AA. From these data we conclude first that at least part of AA is oxidized prior to its uptake, and second that the reduced form of AA and perhaps ascorbyl radicals but not DhAA or its metabolites are the most important forms in mediating cytotoxic reactions in neuroblastoma cells. Furthermore, the results strengthen the previous assumption that AA acts as a pro-oxidant in neuroblastoma cells and supports its use in the treatment of neuroblastoma, especially in combination with existing chemotherapeutics.

UI MeSH Term Description Entries
D009447 Neuroblastoma A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51) Neuroblastomas
D010084 Oxidation-Reduction A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). Redox,Oxidation Reduction
D002250 Carbon Radioisotopes Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes. Radioisotopes, Carbon
D003683 Dehydroascorbic Acid The reversibly oxidized form of ascorbic acid. It is the lactone of 2,3-DIKETOGULONIC ACID and has antiscorbutic activity in man on oral ingestion. Acid, Dehydroascorbic
D004229 Dithiothreitol A reagent commonly used in biochemical studies as a protective agent to prevent the oxidation of SH (thiol) groups and for reducing disulphides to dithiols. Cleland Reagent,Cleland's Reagent,Sputolysin,Clelands Reagent,Reagent, Cleland,Reagent, Cleland's
D005978 Glutathione A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001205 Ascorbic Acid A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. Vitamin C,Ascorbic Acid, Monosodium Salt,Ferrous Ascorbate,Hybrin,L-Ascorbic Acid,Magnesium Ascorbate,Magnesium Ascorbicum,Magnesium di-L-Ascorbate,Magnorbin,Sodium Ascorbate,Acid, Ascorbic,Acid, L-Ascorbic,Ascorbate, Ferrous,Ascorbate, Magnesium,Ascorbate, Sodium,L Ascorbic Acid,Magnesium di L Ascorbate,di-L-Ascorbate, Magnesium
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D017599 Neuroectodermal Tumors Malignant neoplasms arising in the neuroectoderm, the portion of the ectoderm of the early embryo that gives rise to the central and peripheral nervous systems, including some glial cells. Neuroectodermal Tumor,Tumor, Neuroectodermal,Tumors, Neuroectodermal

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