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L-ascorbic acid-induced DNA strand breaks and cross links in human neuroblastoma cells
Abstract:
The effect of high concentrations of L-ascorbic acid on the in vivo and in vitro growth of human neuroblastoma has been investigated. Directly implemented into cell culture it decreased the DNA, RNA and protein synthesis, and mitosis of neuroblastoma cells, without affecting normal neuronal cells. In vivo treatment of young nude mice bearing human neuroblastoma with 500 mg/kg L-ascorbic acid for the first 10 days markedly inhibited the growth of tumor mass. As determined by alkaline elution, both DNA strand breaks and DNA cross links were observed in tumor cells treated with 1 X 10(-4) M L-ascorbic acid for 2 h. DNA-DNA and DNA-protein cross links in cells treated with L-ascorbic acid were revealed by the proteinase potassium assay. The results indicated that L-ascorbic acid can be a very effective and selective agent against human neuroblastoma.
Insights
High concentrations of L-ascorbic acid effectively inhibit human neuroblastoma growth in vitro and in vivo. This vitamin C derivative selectively targets neuroblastoma cells, causing DNA damage without harming normal neurons.
Area of Science:
- Oncology
- Biochemistry
- Cell Biology
Background:
- Neuroblastoma is a pediatric cancer originating from immature nerve cells.
- High concentrations of L-ascorbic acid are being investigated for their therapeutic potential.
Purpose of the Study:
- To investigate the effects of high L-ascorbic acid concentrations on human neuroblastoma growth.
- To determine the selectivity of L-ascorbic acid against neuroblastoma cells.
Main Methods:
- In vitro studies on neuroblastoma cell cultures assessing DNA, RNA, protein synthesis, and mitosis.
- In vivo studies using nude mice xenograft models of human neuroblastoma.
- Alkaline elution and proteinase K assay to detect DNA damage and cross-links.
Main Results:
- L-ascorbic acid decreased DNA, RNA, and protein synthesis, and mitosis in neuroblastoma cells.
- In vivo treatment significantly inhibited tumor mass growth in mice.
- L-ascorbic acid induced DNA strand breaks and DNA-DNA/DNA-protein cross-links in tumor cells.
Conclusions:
- L-ascorbic acid demonstrates potent anti-neuroblastoma activity.
- The compound exhibits selectivity, sparing normal neuronal cells.
- L-ascorbic acid is a promising selective agent against human neuroblastoma.