Abstract
We previously reported that caffeine inhibited adriamycin efflux in Ehrlich ascites carcinoma cells and it would be of value as biochemical modulator of adriamycin. In this study, the transport of adriamycin was investigated, in vitro, as a part of a study to clarify the mechanism of adriamycin efflux inhibition by caffeine, using metabolites of caffeine. The mechanism of the effect of caffeine on adriamycin antitumor activity, in vivo, was also studied.1, 3, 7-Trimethyluric acid did not inhibit adriamycin efflux on tumor cells in vitro, and did not enhance the antitumor activity of adriamycin in vivo. Furthermore, 1, 7-dimethylxanthine, which is the major caffeine metabolite in human, promoted adriamycin efflux. However, theobromine would be of value as biochemical modulator of adriamycin from in vitro and in vivo study. Moreover, when the temperature of incubation was 20°C, the inhibition of adriamycin efflux by caffeine did not observed, It suggest that some enzymes system in the cell will be related to adriamycin efflux. However, since ouabain had no effect on the adriamycin efflux, Na+, K+-ATPase do not concern with adriamycin efflux. And in medium without glucose, there were no effects of caffeine. It suggested that energy which supply from glucose is needed to adriamycin transport. These results suggest that the effect of caffeine, as biochemical modulator, is not due to metabolite of caffeine. And the transport of adriamycin and effects of caffeine is considered to be related to some enzymes and to some energy consumptions in the cell.
