Lode H N, Bruchelt G, Zinsser D, Baader S L, Rieth A G, Schade U F, Niethammer D
Children's Hospital, Department of Hematology and Oncology, University of Tuebingen, Germany.
Anticancer Res. 1994 Sep-Oct;14(5A):1903-6.
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.
神经母细胞瘤及其他恶性细胞通常含有大量富含铁的铁蛋白和过氧化氢，因此可能是抗坏血酸（AA）促氧化作用的潜在靶点，例如通过脂质过氧化（LPO）产生细胞毒性产物。首先以红细胞血影作为模型系统，研究了过氧化氢和铁（以游离形式或与铁蛋白结合的形式）对AA诱导的LPO的影响。这些实验结果表明，AA不仅在存在游离可利用铁的情况下诱导LPO，而且在存在铁蛋白的情况下也诱导LPO。同样，AA在细胞内铁蛋白水平升高的神经外胚层SK-N-LO细胞中诱导显著的LPO。使用铁蛋白免疫缀合物也可以观察到铁蛋白在AA存在下对SK-N-LO细胞的这些LPO促进作用：为此，将铁蛋白与人单克隆抗体（MAb-铁蛋白）结合，该单克隆抗体识别神经节苷脂GD2，其大量存在于SK-N-LO和许多神经母细胞瘤细胞的细胞表面。我们得出结论，AA的促氧化作用可与化疗或MAb-铁蛋白免疫缀合物联合用于治疗富含铁蛋白的神经母细胞瘤。
