Dipyridamole potentiates adriamycin cytotoxicity by a mechanism other than inhibiting nucleoside uptake

Nitrobenzylthioinosine (NBTI) and dipyridamole (DP) are competitive inhibitors of cellular nucleoside uptake. Although combined treatment of HeLa cells with adriamycin (ADM) and DP enhanced ADM cytotoxicity in cell growth and clonogenic assays, the combination of ADM and noncytostatic levels (less than 1 microM) of NBTI did not change the cytotoxic potential of ADM in vitro. DP enhanced the inhibition of clonogenicity by ADM, even in nucleoside-enriched mediums. These results suggest that the synergy between ADM and DP was hardly due to the inhibition of nucleoside uptake by DP, but was due to the enhancement of intracellular ADM accumulation by DP.