PROMOTION OF DAUNORUBICIN UPTAKE AND TOXICITY BY THE CALCIUM-ANTAGONIST TIAPAMIL AND ITS ANALOGS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 69  (6) , 673-676
Abstract
Studies were performed with the anthracycline-responsive P388 murine leukemia cell line, and with P388/ADR, a subline selected for doxorubicin resistance. In the P388/ADR cell line, the observed 100-fold daunorubicin resistance is associated with an outward drug transport system which can be inhibited by several Ca antagonists, e.g., verapamil and nifedipine. An examination of compounds related to tiapamil, a verapamil analog, has identified a structure which is 10-fold more effective than verapamil at potentiating anthracycline accumulation and responsiveness in P388/ADR cells. At no nontoxic level of any Ca antagonist examined was it possible to wholly reverse the degree of daunorubicin resistance found in the P388/ADR cell line.