Amphotericin B: a biological response modifier in targeting against the salvage pathways.
Dipyridamole, a nucleoside transport inhibitor which blocks the rescue effect of exogenous nucleosides, is a compound of interest for use in combination with antimetabolites of de novo purine and pyrimidine biosynthesis. This study has provided evidence that the dipyridamole inhibitory effect on nucleoside incorporation varied markedly during the course of cell growth in culture. Human colon cancer HT-29 cells in lag and log phases were highly sensitive to the blocking action of dipyridamole on thymidine incorporation with IC50 values of 0.06 and 0.07 microM respectively. In contrast, stationary phase cells were comparatively insensitive to dipyridamole with an IC50 of 46 microM. Amphotericin B restored the sensitivity of stationary phase cells to dipyridamole, lowering the IC50 value for thymidine incorporation to 0.03 microM. A similar pattern was observed for cytidine incorporation. Amphotericin B also enhanced the growth inhibitory action of dipyridamole in stationary phase cells. The combination of amphotericin B and dipyridamole should be potentially useful in cancer chemotherapy.
Zhen
Y S
YS
Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis 46223.
Reardon
M A
MA
Weber
G
G
D000666:Amphotericin B / Q000494:pharmacology*; D002478:Cells, Cultured; D004176:Dipyridamole / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D009705:Nucleosides / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D009705:Nucleosides; D004176:Dipyridamole; D000666:Amphotericin B; D013936:Thymidine