Reversal of the multidrug-resistant phenotype of Chinese hamster ovary cells by L-histidinol.
The amino acid analogue L-histidinol reverses the multidrug-resistance (MDR) attribute of the colchicine-resistant (CHR) variant CHRC5, a Chinese hamster ovary cell line that overexpresses a plasma membrane-associated glycoprotein and is resistant to colchicine (CH), daunorubicin, and vinblastine sulfate (VS). The level of cell kill achieved in CHRC5 cells by combinations of L-histidinol and either daunorubicin or CH approached that achieved in AUXB1 parent cells by these two drugs, whereas L-histidinol-VS combinations killed even more CHRC5 cells than VS in the parental line. The capacity of L-histidinol to reverse the MDR phenotype of the CHRC5 line was time and dose dependent and was eliminated by the addition of a twofold molar excess of L-histidine. The reversal of the MDR trait by L-histidinol appears to be independent of the drug uptake mechanism.
Warrington
R C
RC
Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada.
Fang
W D
WD
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D002469:Cell Separation; D003078:Colchicine / Q000494:pharmacology; D003630:Daunorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D005434:Flow Cytometry; D006641:Histidinol / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D010641:Phenotype; D014747:Vinblastine / Q000494:pharmacology
D000970:Antineoplastic Agents; D007093:Imidazoles; D006641:Histidinol; D014747:Vinblastine; D003078:Colchicine; D003630:Daunorubicin