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

Abstract

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.

• Authors: R C Warrington, W D Fang, L U Zhang
• Journal: Anticancer research (Anticancer Res) 1996 Nov-Dec Vol. 16 Issue 6B Pg. 3641-6 ISSN: 0250-7005 [Print] Greece
• PMID: 9042235 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Imidazoles
• Protein Synthesis Inhibitors
• Histidinol
• Cisplatin

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Cell Line (drug effects)
• Cisplatin (pharmacology)
• Dogs
• Dose-Response Relationship, Drug
• Drug Interactions
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Histidinol (pharmacology)
• Imidazoles (pharmacology)
• Protein Synthesis Inhibitors (pharmacology)