Enhancement of adriamycin cytotoxicity in sensitive and resistant sublines of human tumor cells by calcium antagonists.
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.
Mircheva
J
J
Dept. of Experimental Therapy of Tumors, Medical Academy, Sofia, Bulgaria.
Tsuruo
T
T
D000470:Alkaloids / Q000494:pharmacology; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology; D052117:Benzodioxoles
D000470:Alkaloids; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D004317:Doxorubicin; D014700:Verapamil; C006947:cepharanthine; D052117:Benzodioxoles