Cellular pharmacology of anthracycline resistance and its circumvention.
Adriamycin-resistant cells express a multiple drug resistance phenotype characterized by cross-resistance to compounds of related and unrelated structure and action. The pharmacological determinants of this resistance, such as decreased drug uptake and/or decreased drug retention, are associated with biochemical alterations in the cells. To overcome multiple drug resistance, a calcium-channel blocking agent, verapamil, was used, which acted by increasing the amount of drug retained in resistant cells and consequently enhanced the cytotoxic effectiveness. The basis for this enhanced retention and cytotoxicity is not known. Whether these compounds sensitize the cells to the action of, or potentiate the effect of, anticancer drugs remains to be determined. The preliminary data tend to support the second possibility.
Tapiero
H
H
Fourcade
A
A
Munck
J N
JN
Zwingelstein
G
G
Lampidis
T J
TJ
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D002478:Cells, Cultured; D004351:Drug Resistance; D004357:Drug Synergism; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D009279:Naphthacenes / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D014700:Verapamil / Q000008:administration & dosage
D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; D014700:Verapamil