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.
Warrington
R C
RC
Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada.
Fang
W D
WD
Zhang
L U
LU
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006641:Histidinol / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*
D000970:Antineoplastic Agents; D007093:Imidazoles; D011500:Protein Synthesis Inhibitors; D006641:Histidinol; D002945:Cisplatin