Intracellular boron accumulation in CHO-K1 cells using amino acid transport control

• Published in: Applied radiation and isotopes Vol. 88; pp. 99 - 103
• Main Authors: Sato, Eisuke, Yamamoto, Tetsuya, Shikano, Naoto, Ogura, Masato, Nakai, Kei, Yoshida, Fumiyo, Uemae, Yoji, Takada, Tomoya, Isobe, Tomonori, Matsumura, Akira
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-06-2014
• Subjects: Amino acid transport; Amino Acid Transport Systems - pharmacokinetics; Animals; Boron Compounds - administration & dosage; Boron Compounds - chemistry; Boron Compounds - pharmacokinetics; Boron neutron capture therapy (BNCT); Boron Neutron Capture Therapy - methods; Chinese hamster ovary cells; CHO Cells; Cricetinae; Cricetulus; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; l-p-Boronophenylalanine (BPA); Metabolic Clearance Rate; Phenylalanine - administration & dosage; Phenylalanine - analogs & derivatives; Phenylalanine - chemistry; Phenylalanine - pharmacokinetics; Tyrosine - administration & dosage; Tyrosine - chemistry; Tyrosine - pharmacokinetics; l-p-Boronophenylalanine (BPA); Amino acid transport; Boron neutron capture therapy (BNCT); Chinese hamster ovary cells
• ISSN: 0969-8043; 1872-9800
• DOI: 10.1016/j.apradiso.2013.12.015

BPA used in BNCT has a similar structure to some essential amino acids and is transported into tumor cells by amino acid transport systems. Previous study groups have tried various techniques of loading BPA to increase intracellular boron concentration. CHO-K1 cells demonstrate system L (LAT1) activity and are suitable for specifying the transport system of a neutral amino acid. In this study, we examined the intracellular accumulation of boron in CHO-K1 cells by amino acid transport control, which involves co-loading with L-type amino acid esters. Intracellular boron accumulation in CHO-K1 cells showed the greatest increased upon co-loading 1.0mM BPA, with 1.0mM l-Tyr-O-Et and incubating for 60min. This increase is caused by activation of a system L amino acid exchanger between BPA and l-Tyr. The amino acid esters are metabolized to amino acids by intracellular hydrolytic enzymes that increase the concentrations of intracellular amino acids and stimulate exchange transportation. We expect that this amino acid transport control will be useful for enhancing intracellular boron accumulation.
•We examined optimal l-p-boronophenylalanine (BPA) loading in CHO-K1 cells.•Optimal BPA loading parameters were 1.0mM and incubation for 60min.•Intracellular boron accumulation increased upon co-loading BPA with l-Tyr-O-Et.•Optimal l-Tyr-O-Et loading parameters were 1.0mM and incubation for 60min.•Co-loading BPA with l-Tyr-O-Et can increase intracellular boron accumulation.