Ascorbic acid induces lipid peroxidation on neuroectodermal SK-N-LO cells with high endogenous ferritin content and loaded with MAb-ferritin immunoconjugates.
Neuroblasma-and other malignant cells often contain elevated amounts of iron-rich ferritin and H2O2 and may therefore be a potential target for pro-oxidative effects of ascorbic acid (AA), generating cytotoxic products e.g. by lipid peroxidation (LPO). The influence of H2O2 and iron, either in its free form or bound to ferritin, on AA induced LPO was first investigated using erythrocyte ghosts as a model system. Results of these experiments showed that AA induced LPO not only in the presence of free available iron but also in the presence of ferritin. Similarly, AA induced significant LPO in neuroectodermal SK-N-LO cells with elevated intracellular ferritin levels. These LPO promoting effects of ferritin in the presence of AA on SK-N-LO cells could also be observed using ferritin-immunoconjugates: for this purpose, ferritin was bound to human monoclonal antibodies (MAb-ferritin) recognizing ganglioside GD2 which is present in large quantities on cell surfaces of SK-N-LO and many neuroblastoma cells. We conclude that the pro-oxidative effects of AA could be exploited in the treatment of ferritin rich neuroblastoma in combination with chemotherapy or with MAb-ferritin immunoconjugates.
Children's Hospital, Department of Hematology and Oncology, University of Tuebingen, Germany.
H N
HN
Lode
G
G
Bruchelt
D
D
Zinsser
S L
SL
Baader
A G
AG
Rieth
U F
UF
Schade
D
D
Niethammer
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism* / Q000494:pharmacology*; D005732:Gangliosides / Q000276:immunology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D000922:Immunotoxins / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008954:Models, Biological; D009447:Neuroblastoma / Q000378:metabolism; D017599:Neuroectodermal Tumors / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D005732:Gangliosides; D000922:Immunotoxins; D017392:Thiobarbituric Acid Reactive Substances; C019403:ganglioside, GD2; D005293:Ferritins; D006861:Hydrogen Peroxide; D007501:Iron; D001205:Ascorbic Acid