Administration of a hypoxic cell sensitizer, 6-FP, enhance of radiation-induced apoptosis in human carcinoma

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Hypoxia governs cellular adaption to oxygen deficiency by regulating tumor-relevant genes involved in energy metabolism, angiogenesis, cell proliferation and apoptosis. Heterogeneity of tumor was investigated with respect to radiosensitizing efficiencies of a hypoxic cell sensitizer, 6-FP(6-formylpterin), a metabolite of folic acid. In contrast to apoptosis induced by extracellular H_2O_2, only a few studies have examined apoptosis induced by intracellular H_2O_2. Oxidative stress is known to induce many forms of apoptosis, and as its common mediator, intracellular reactive oxygen species play a cardinal role in oxidative stress-induced apoptosis. Here we used an intracellular H_2O_2 inducer, 6-FP, which is a member of the pterin family. Tumor cells and normal cells were treated with 6-FP before expose of X-ray and then irradiated. We collected the cells and colony efficiency and survival fraction were analyzed. The results showed that the tumor cells were higher colony efficiency than the normal cells, and the cells with both X-ray irradiation and 6-FP treatment were significantly lower survival rate. These results suggested that 6-FP may have radioprotective effect for the tumor cells and the incidated that 6-FP enhances the apoptosis by the radiation-induced and 6-FP may be effective use of the drug.