Enhancement of adriamycin cytotoxicity in sensitive and resistant sublines of human tumor cells by calcium antagonists

Abstract

The effect of the calcium antagonists cepharanthine and verapamil on adriamycin-induced cytotoxicity against sensitive (K 562 and Ov 2780) and resistant (K 562/ADM and AD 10) sublines of human tumor cells was evaluated. Nontoxic concentrations of cepharanthine moderately enhanced adriamycin cytotoxicity against sensitive sublines (2.1-2.5 fold). A significant enhancement (13-26 fold) of drug cytotoxicity was observed when resistant cells were treated with a combination of cepharanthine and adriamycin. The calcium influx blocker verapamil (used for comparison) also enhanced adriamycin cytotoxicity, although to a lesser extent. The fact that enhancement was 6-10 fold greater in resistant then in sensitive cells, as well as the loss of biphasic properties of adriamycin on dose-response curves after combined treatment, indicate that cepharanthine may play a role in overcoming drug resistance in some tumor cells.