Atypical multiple drug resistance in a human leukemic cell line selected for resistance to teniposide (VM-26).
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 report here the characterization of a human leukemic cell line (CEM/VM-1) with "atypical" multiple drug resistance: despite resistance and cross-resistance to etoposide, anthracyclines, mitoxantrone, and 4'-[(9-acridinyl)amino]methanesulphon-m-anisidide (mAMSA), these cells retain sensitivity to the Vinca alkaloids. Further, even though this cell line is approximately equal to 40-fold cross-resistant to the cytotoxic effect of etoposide (VP-16), it is similar to drug-sensitive CEM cells in the cellular pharmacology of [3H]VP-16 as determined by zero time binding, initial influx 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.
Danks
M K
MK
Yalowich
J C
JC
Beck
W T
WT
D002460:Cell Line; D004351:Drug Resistance; D005434:Flow Cytometry; D006801:Humans; D007945:Leukemia, Lymphoid / Q000378:metabolism / Q000473:pathology*; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013713:Teniposide / Q000378:metabolism / Q000494:pharmacology*
D013713:Teniposide; D011034:Podophyllotoxin