Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells

The saponin digitonin, the aglycone digitoxigenin and five cardiac glycosid es were evaluated for cytotoxicity using primary cultures of tumor cells fr om patients and a human cell line panel (representing different cytotoxic d rug-resistance patterns). Of these seven compounds, proscillaridin A was th e most potent (IC50: 6.4-76 nM), followed by digitoxin, and then ouabain, d igoxin, lanatoside C, digitoxigenin and digitonin, Correlation analysis of the log IC50 values for the cell lines in the panel showed that compound cy totoxicity was only slightly influenced by resistance mechanisms that invol ved P-glycoprotein, topoisomerase II, multidrug resistance-associated prote in and glutathione-mediated drug resistance. Digitoxin and digoxin expresse d selective toxicity against solid tumor cells from patients, while proscil laridin A expressed no selective toxicity against either solid or hematolog ical tumor cells. The results revealed marked differences in cytotoxicity b etween the cardiac glycosides, both in potency and selectivity, and modes o f action for cytotoxicity that differ from that of commonly used anticancer drugs. [(C) 2001 Lippincott Williams & Wilkins.].