Effects of nifedipine on cell resistance and cardiac toxicity--in vitro and in vivo experiments.
Nifedipine can enhance the cytotoxicity of antineoplastic drugs. The present paper describes characteristics of sensitive and acquired resistant cells prior to and after transplantation into nude mice and experiments to reverse the acquired resistance to Daunorubicin (DR) by Nifedipine. Resistant cells (HT/DR+) are characterized by prolonged doubling time and diminished drug sensitivity and drug uptake. HT/DR+ cells show a slightly increased number of polyploid cells. These characteristics are not changed after nude mouse transplantation. Nifedipine enhances the intracellular level of Daunorubicin and cytotoxicity in vitro and in vivo in case of HT/DR+ cells. But Nifedipine acts both in vitro and in vivo also on sensitive cells (HT). This could support the hypothesis that Nifedipine increases the toxicity, which could be confirmed by experiments on mice (B6D2F1 strain). But probably the increased incidence of toxic deaths is not due to increased cardiac toxicity. This increase of toxicity could limit the clinical usefulness of the combination of antineoplastic drugs with calcium channel blockers.
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002452:Cell Count; D002460:Cell Line; D002999:Clone Cells; D004273:DNA, Neoplasm / Q000378:metabolism; D003630:Daunorubicin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D004338:Drug Combinations; D004351:Drug Resistance; D005260:Female; D006321:Heart / Q000187:drug effects*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009543:Nifedipine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004338:Drug Combinations; D009543:Nifedipine; D003630:Daunorubicin