Enhancement of cytocidal and antitumor effect of cisplatin by caffeine in human osteosarcoma

A nontoxic dose of caffeine enhanced the cytotoxicity of cisplatin in human osteosarcoma cells (OST strain). Synergistic cytotoxicity was seen in vitro in OST cells when 2 mmol caffeine was added to a nontoxic dose of cisplatin (2 micrograms/ml). Caffeine reduced S-phase, G2/M-phase, and S-and-G2/M-phase accumulation by cisplatin on the DNA histogram, and nuclear fragmentation of tumor cells was frequently observed. Flow cytometric analysis appeared to be useful in assessing the efficacy of the combination of cisplatin and caffeine. The antitumor effect of the combination of cisplatin and caffeine was examined in OST transplanted to BALB/C athymic mice. Regression of the tumor was observed when cisplatin was given at a dose of 10 mg/kg. When 4 mg of caffeine was given once a day for three days after the administration of cisplatin, marked regression of the tumor was observed in groups treated with 5 or 10 mg/kg of cisplatin, without significant weight loss. These results indicate that caffeine enhances the antitumor effect of cisplatin on transplanted osteosarcoma in BALB/C athymic mice.