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.[1]References
- Reversal of the multidrug-resistant phenotype of Chinese hamster ovary cells by L-histidinol. Warrington, R.C., Fang, W.D. J. Natl. Cancer Inst. (1989) [Pubmed]
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