Potentiation of antitumor agents by calcium channel blockers with special reference to cross-resistance patterns.
The calcium channel blockers verapamil, diltiazem, nicardipine, and niludipine potentiated the antitumor activities of mitotic poison antitumor agents, such as vincristine, vinblastine, vindesine, VP16-213, and taxol in P388 leukemia cells resistant to vincristine. The potentiating effect was generally dependent on the extent of cross-resistance seen in the cell line for these drugs. Calcium channel blockers also potentiate the antitumor activities of several DNA-interacting drugs, such as adriamycin, THP-adriamycin, daunomycin, aclacinomycin A, mitomycin C, actinomycin D, mitoxantrone, and nogalamycin derivatives in P388 leukemia resistant to adriamycin. Greater potentiation was observed for those antitumor agents to which the ADM-resistant cell line had become markedly cross-resistant, with the exception of the nogalamycin derivatives. Only a two-fold enhancement was observed for mitomycin C and aclacinomycin, as the cell line was only weakly cross-resistant to these agents. These results suggest the potential for therapeutic gain through the use of calcium channel blockers in combination with classic chemotherapeutic agents.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002460:Cell Line; D004317:Doxorubicin / Q000627:therapeutic use; D004351:Drug Resistance; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007941:Leukemia P388 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D051379:Mice; D014700:Verapamil / Q000494:pharmacology; D014750:Vincristine / Q000627:therapeutic use
D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D014750:Vincristine; D004317:Doxorubicin; D014700:Verapamil