구강 편평세포암종 KB세포에서 아미노산 수송억제제 BCH에 의한 세포성장 억제

Abstract

Amino acid transporters play an important role in supplying nutrients to normal and cancer cells for cell proliferation. System L is a major transport system responsible for the N -independent, large neutral amino acids including several essential amino acids. L-type amino acid transporter 1 (LAT1), an isoform of system L amino acid transporter, is highly expressed presumably to support their continuous growth and proliferation in malignant tumors. 2-Aminobicyclo- (2,2,1) -heptane-2-carboxylic acid (BCH) is a model compound for study of amino acid transporter as a system L selective inhibitor. In the present study, we examined whether BCH induced growth inhibition in KB human oral squamous carcinoma cell line or not. The uptake of L-［ C］leucine by KB cells is inhibited by BCH in a concentration dependent manner with a Ι value of 75.36.2 and a value of 98.7 4.1 . The growth of KB cells is inhibited by BCH in time dependent manner and concentration dependent manner with a Ι value of 11.1 0.8 mM. In the DNA of KB cells treated with the various concentrations and various periods of BCH, the characteristic ladders associated with DNA fragmentation were not observed. These results suggest that BCH inhibits the growth of KB oral epidermoid carcinoma cells through the inhibition of transport of neutral amino acids into cells without DNA break down. This phenomenon will be a new rationale for anti-cancer therapy.y.