Modulation of in vitro response to adriamycin by verapamil in murine P388 leukaemia, Ehrlich ascites carcinoma and sarcoma 180.
Experiments were carried out in vitro on adriamycin (ADR) accumulation and cytotoxicity alone and in combination with calcium channel antagonist, verapamil (VRP), in ascites murine tumour models of Ehrlich carcinoma (EAC), sarcoma 180 (S180) and P388 lymphocytic leukaemia (P388). The cytotoxicity was assayed as the inhibition of [3H]-thymidine incorporation into the cellular DNA. ADR, a broad-spectrum anticancer drug, at a concentration of 10 micrograms/ml showed a cytotoxic effect in the order S180 greater than P388 greater than EAC. VRP alone exhibited the DNA synthesis inhibiting activity. The enhanced DNA biosynthesis inhibition of ADR along with VRP was maximal in S180 and marginal in P388 and EAC. The ADR retention after 3 hr of incubation in these tumour models correlated with the cytotoxicity. VRP enhanced the accumulation of ADR in all these cell lines. The property of potentiation in the activity and accumulation of ADR in these tumours exposed to a non-toxic concentration of VRP can best be utilized in cancer chemotherapy where the massive cytotoxic therapy, with a single large dose of ADR, can be substituted with a low dose, along with this drug-response modulator, for better therapeutic results.
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D003864:Depression, Chemical; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D007941:Leukemia P388 / Q000378:metabolism*; D007942:Leukemia, Experimental / Q000378:metabolism*; D051379:Mice; D012510:Sarcoma 180 / Q000378:metabolism*; D013936:Thymidine / Q000037:antagonists & inhibitors / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*
D004273:DNA, Neoplasm; D004317:Doxorubicin; D014700:Verapamil; D013936:Thymidine