A study on overcoming the drug resistance to sarcoma

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In this study the combined effect of anticancer agents and caffeine, which inhibits DNA repair, on human sarcomas was examined with various assay techniques. In human tumor clonogenic assay, the combined use of caffeine produced synergistic effects with four DNA-damaging agents (cisplatin, mitomycin C, cyclophosphamide and adriamycin). Particularly by the combination of cisplatin with caffeine, marked synergistic effects were observed in 14 out of 18 specimens (78%) of fresh human tumor specimens. Caffeine markedly increased the cytocidal effect of cisplatin following mitosis. At this time, the accumulation of S and G2/M phase was reduced on the DNA histogram, and nuclear fragmentations of tumor cells were frequently observed. In assay, using athymic mice, the combination of caffeine and cisplatin showed prominent antitumor effect without significant toxicity. These findings suggest the possibility that caffeine could be a useful drug capable of overcoming drug resistance to sarcomas, as caffeine enhanced the effect of DNA-damaging agents.