Reversal of the Multidrug-Resistant Phenotype of Chinese Hamster Ovary Cells by L-Histidinol

Abstract

The amino acid analogue L-histidinol reverses the multidrug-resistance (MDR) attribute of the colchicine-resistant (CH^R) variant CH^RC5, a Chinese hamster ovary cell line that overexpresses a plasma membrane-associated glyco-protein and is resistant to colchicine (CH), daunorubicin, and vinblastine sulfate (VS). The level of cell kill achieved in CH^RC5 cells by combinations of L-histidinol and either daunorubicin or CH approached that achieved in AUXB1 parent cells by these two drugs, whereas L-histodinol-VS combinations killed even more CH^RC5 cells than VS in the parental line. The capacity of L-histidinol to reverse the MDR phenotype of the CH^RC5 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.