Article
Nitric oxide effects on C6 glioma cells
Stickstoffmonoxideffekte in C6-Gliomzellen
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Published: | April 23, 2004 |
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Outline
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Objective
Nitric oxide (NO) influences vascular permeability and has cytotoxic, chemo- and radiosensitizing effects. Injection of the NO donor Proli/NO results in disruption of the blood-tumor barrier in C6 gliomas leading to long-term survival in rats after concomitant administration of Proli/NO and Carboplatin chemotherapy. To test for cytotoxic or chemosensitizing effects, we investigated the effect of the NO donors Proli/NO, Spermine-NO, Diethylamine-NO(DEA/NO), sodium nitrite and Carboplatin on C6 cells in vitro.
Methods
C6 cells were cultured up to 70-80% cell density and incubated with the NO donors or nitrite at doses between 10-12 and 10-2M for 36h. C6 cells were then exposed to the NO donors or nitrite plus Carboplatin or to Carboplatin alone. The IC50 rate for Carboplatin was 500 µM in C6 cells. All experiments were performed in triplicates. Cell Viability (%) was calculated after trypan blue staining, the percentage of viable cells was compared by ANOVA.
Results
Exposure of C6 cells to 10-2 M nitrite, spermine-NO and DEA-NO was directly cytotoxic(p<0.005) whereas lower doses did not significantly influence cell viability. Concomitant incubation with carboplatin did not enhance the cytotoxicity of the drug(47±9% carboplatin, 48±16% carboplatin+Proli/NO, 45%±4% carboplatin+nitrite, 36±12% carboplatin+spermine-NO, 36±3% carboplatin+DEA/NO, p>0.005).
Conclusions
Enhanced efficacy of i.v. Carboplatin chemotherapy after Proli/NO infusion in C6 gliomas is due to an increased uptake of carboplatin into the tumor as the NO donors or nitrite lacked chemosensitizing effects in vitro. High doses of NO donors or sodium nitrite have cytotoxic effects on C6 cells in vitro requiring further investigation.