Potentiation of cytotoxicity of mitoxantrone toward CHO-K1 cells in vitro by dipyridamole.
Dipyridamole (DP), a clinically used vasodilator and an antiplatelet compound, augmented the activity of the anticancer drug mitoxantrone (MXN) toward chinese hamster ovary (CHO-K1) cells in culture. Clonogenic assays indicated that DP (1.0, 2.5, and 5.0 microM) decreased the survival of cells treated with MXN (5 to 25 nM) in a dose-dependent manner. Further, DP (1 and 5 microM) decreased the MXN concentration required for 50% inhibition of cell growth from 3.2 to 1.8 and from 3.0 to 0.5 nM, respectively, over a period of 3 days. DP (10 microM) increased the accumulation of MXN by 1.8-fold in exponentially growing cells exposed to MXN. The enhanced levels of MXN in CHO-K1 cells in the presence of the chemosensitizer may account for the potentiation of MXN-cytotoxicity by DP.
Desai
P B
PB
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of South Carolina, Columbia 29208.
Sridhar
R
R
D000818:Animals; D016466:CHO Cells / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D006224:Cricetinae; D004176:Dipyridamole / Q000633:toxicity*; D004357:Drug Synergism; D008942:Mitoxantrone / Q000633:toxicity*
D004176:Dipyridamole; D008942:Mitoxantrone