ATYPICAL MULTIPLE-DRUG RESISTANCE IN A HUMAN-LEUKEMIC CELL-LINE SELECTED FOR RESISTANCE TO TENIPOSIDE (VM-26)

  • 1 March 1987
    • journal article
    • research article
    • Vol. 47  (5) , 1297-1301
Abstract
Resistance to the cytotoxic effects of many natural product drugs after exposure to a single agent is a common observation. The classes of drugs included in the "classic" multiple drug resistance phenotype are Vinca alkaloids, anthracyclines, epipodophyllotoxins, and antibiotics. We reported here the characterization of a human leukemic cell line (CEM/VM-1) with "atypical" multiple drug resistance: despite resisatnce and cross-resistance to etoposide, anthracyclines, mitoxantrone, and 4''[(9-acridinyl)amino]methanesulphon-m-anisidide (mAMSA), these cells reaction sensitvity to the Vinca alkaloids. Further, even though this cell line is 40-fold cross-resistant to the cytotoxic effect of etoposide (VP-16), it similar to drug-sensitive CEM cells in the cellular pharmacology of [H]VP-16 as determined by zero time binding, initial infux rate, steady state drug concentration, and unidirectional efflux. Our studies suggest that the resistance of CEM/VM-1 cells to epipodophyllotoxins is due to an altered interaction between drug and its cellular target(s) by a mechanism unrelated to the decreased cellular concentration of drug associated with the "classic" multiple drug resistance phenotype.