ANTITUMOR ACTIVITY OF SODIUM ASCORBATE AGAINST NEUROBLASTOMA CELL LINES IN VITRO

Sodium ascorbate, at millimolar concentrations, induces apoptosis of neuroblastoma cell lines in vitro. The caspase cascade is activated following treatment with ascorbate, as assessed by fluorescence assay with the pan-caspase substrate z-VAD-fmk. Sodium ascorbate down-modulates CD71 (transferrin receptor) membrane expression, although overall (membrane and cytoplasmic) expression is not significantly affected. Since NB cells are strongly dependent on iron supply, it is likely that redistribution of CD71 within cellular compartments interferes with a correct iron metabolism, giving rise to apoptosis. The time- and dose-dependence, as well as the extent of the effects of sodium ascorbate on NB cells is likely to depend upon differences in its catabolism and the intensity of CD71 recycling and membrane re-expression among the different NB cell lines. Due to its lack of overt toxicity, high-dose sodium ascorbate can be considered as an additional drug in the traditional therapeutic schedules for NB.