MECHANISM OF CAFFEINE MODULATION OF THE ANTITUMOR-ACTIVITY OF ADRIAMYCIN

We examined the effects of a combination of adriamycin (ADR) and caffe ine on DNA and protein biosynthesis and on the activities of DNA polym erase alpha and beta in normal and tumor tissue. The decrease in DNA a nd protein biosynthesis in tumor produced by caffeine combined with AD R were 2.5 and 2.4 times greater, respectively, compared with ADR alon e. The combination of caffeine and ADR enhanced the decrease in DNA po lymerases activities in the tumor which was induced by ADR, the decrea ses being 1.8 and 1.6 times greater, respectively, than that of ADR al one. In contrast, these ADR-induced changes in normal tissues were not enhanced by the combination with caffeine. The combination with caffe ine had no effect on ADR concentration in normal tissues, but in the t umor, it increased the ADR concentration to 2.1 times that of ADR alon e. In vitro, ADR efflux from Ehrlich ascites carcinoma cells was signi ficantly inhibited by exposure to caffeine. These findings indicate th at the effect of caffeine on ADR concentration in the cell plays an im portant role in the mechanism by which caffeine enhances ADR antitumor activity.