L-histidinol reverses resistance to cisplatinum and other antineoplastics in a tumorigenic epithelial cell line.

L-Histidinol protects normal cells from various anticancer drugs, while enhancing the toxicity of the same agents in drug-sensitive and multidrug-resistant tumor cells. Here, we report that L-histidinol circumvents a novel form of multiple-drug resistance in the MDCK-T1 line, a tumorigenic derivative of the phenotypically-normal Madin-Darby canine kidney (MDCK) epithelial cell line. Clonogenic cells survival assays showed that, compared to the parental MDCK line, the MDCK-T1 line was resistant to 1,3-bis(2-chloroethyl)-1-nitrosourea (approximately 15 fold), to cisplatinum (approximately 10 fold), to 5-fluorouracil (approximately 10-fold) and to cytosine arabinoside (approximately 15-fold). L-Histidinol reversed the resistance of MDCK-T1 cells to these anticancer drugs while protecting the parental MDCK line from these agents. These studies indicate that L-histidinol reverses a unique form of drug-resistance in MDCK-T1 cells by a mechanism dependent upon protein synthesis inhibition.