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.
Kusumoto
H
H
Cancer Center, Kyushu University Hospital, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Maehara
Y
Y
Anai
H
H
Kumashiro
R
R
Sugimachi
K
K
D001692:Biological Transport; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D004176:Dipyridamole / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D009705:Nucleosides / Q000378:metabolism*; D014410:Tumor Stem Cell Assay
D009705:Nucleosides; D004176:Dipyridamole; D004317:Doxorubicin