Promotion of daunorubicin uptake and toxicity by the calcium antagonist tiapamil and its analogs.
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 calcium antagonists, eg, verapamil and nifedipine. An examination of compounds related to tiapamil, a verapamil analog, has identified a structure which is tenfold more effective than verapamil at potentiating anthracycline accumulation and responsiveness in P388/ADR cells. At no nontoxic level of any calcium antagonist examined was it possible to wholly reverse the degree of daunorubicin resistance found in the P388/ADR cell line.
D000818:Animals; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D003630:Daunorubicin / Q000009:adverse effects / Q000378:metabolism*; D004351:Drug Resistance; D007941:Leukemia P388 / Q000378:metabolism; D051379:Mice; D011437:Propylamines / Q000494:pharmacology*; D013976:Tiapamil Hydrochloride
D011437:Propylamines; D013976:Tiapamil Hydrochloride; D003630:Daunorubicin