Abstract
BackgroundNeuroblastoma (NB) is an extra-cranial solid tumour of childhood. In spite of the good clinical response to first-line therapy, complete eradication of NB cells is rarely achieved. Thus, new therapeutic strategies are needed to eradicate surviving NB cells and prevent relapse. Sodium ascorbate has been recently reported to induce apoptosis of B16 melanoma cells through down-regulation of the transferrin receptor, CD71. Since NB and melanoma share the same embryologic neuroectodermal origin, we used different human NB cell lines to assess whether the same findings occurred.ResultsWe could observe dose- and time-dependent induction of apoptosis in all NB cell lines. Sodium ascorbate decreased the expression of CD71 and caused cell death within 24 h. An increase in the global and specific caspase activity took place, as well as an early loss of the mitochondrial transmembrane potential. Moreover, intracellular iron was significantly decreased after exposure to sodium ascorbate. Apoptotic markers were reverted when the cells were pretreated with the iron donor ferric ammonium citrate (FAC), further confirming that iron depletion is responsible for the ascorbate-induced cell death in NB cells.ConclusionSodium ascorbate is highly toxic to neuroblastoma cell lines and the specific mechanism of vitamin C-induced apoptosis is due to a perturbation of intracellular iron levels ensuing TfR-downregulation.
Highlights
Neuroblastoma (NB) is an extra-cranial solid tumour of childhood
Effect of Sodium Ascorbate on neuroblastoma cell lines We first investigated whether sodium ascorbate had cytotoxic effects on neuroblastoma cell lines
Intracellular iron level In order to find the possible mechanism of neuroblastoma cells apoptosis induced by vitamin C, we investigated whether this phenomenon was correlated with change in the intracellular iron levels; we treated HTLA230 and SH-SY5Y for 24 hours with 1.5, and 2 mM sodium ascorbate and iron level was measured
Summary
In spite of the good clinical response to first-line therapy, complete eradication of NB cells is rarely achieved. Sodium ascorbate has been recently reported to induce apoptosis of B16 melanoma cells through down-regulation of the transferrin receptor, CD71. Since NB and melanoma share the same embryologic neuroectodermal origin, we used different human NB cell lines to assess whether the same findings occurred. Neuroblastoma is the most common solid extracranial tumor of childhood [1]. This tumor has long fascinated clinicians and biologists due to its enigmatic behaviour. It has been recently reported that vitamin C is effective in a large panel of tumor cell lines [3,4]. The discrepancy obtained in research and analysis by many authors was principally due to the different dose and route of administration of vitamin C and to its plasma concentration [5,6,7]
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