Ohtsubo, T., Igawa, H., Saito, T., Matsumoto, H., Park, H. J., Song, C. W., Kano, E. and Saito, H. Enhancement of Cell Killing by Induction of Apoptosis after Treatment with Mild Hyperthermia at 42°C and Cisplatin. Radiat. Res. 156, 103–109 (2001).

We examined the interactive effects of cisplatin (1.0 μg/ml) combined with hyperthermia on cell killing and on the induction of apoptosis in IMC-3 human maxillary carcinoma cells. The cytotoxic effects of hyperthermia on IMC-3 cells at 44°C were greater than at 42°C, as has been reported for many other cells. The induction of apoptosis, DNA fragmentation and poly(ADP-ribose) polymerase cleavage were greater after hyperthermia at 44°C for 30 min compared with treatment at 42°C for 105 min, even though both of these heat doses were isoeffective in reducing cell survival to 50%. Treatment with cisplatin at 37°C for up to 120 min did not result in cytotoxicity or the induction of apoptosis. The enhancement ratio for treatment with cisplatin at 42°C was greater than that at 44°C. More apoptosis was induced after the treatment with cisplatin at 42°C compared to treatment with cisplatin at 44°C. Taking these findings together, the combination of cisplatin and hyperthermia at 42°C appeared to be more effective than cisplatin with hyperthermia at 44°C for the induction of apoptosis in IMC-3 cells.