JPH203,an L-type amino acid transporter 1-selective compound,induces apoptosis of YD-38 human oral cancer cells

Compared to most normal cells that express l-type amino acid transporter 2,l-type amino acid transporter 1 is highly expressed in cancer cells and presumed to support their elevated growth and proliferation. this study examined jph203,a potent and selective l-type amino acid transporter 1 inhibitor,and its ability to suppress yd-38 human oral cancer cell growth. the yd-38 cells express l-type amino acid transporter 1 with its associating protein 4f2 heavy chain,but not l-type amino acid transporter 2. jph203 and bch,a non-selective l-type amino acid transporter inhibitor,completely inhibited l-leucine uptake in yd-38 cells. as expected,the intrinsic affinity of jph203 to inhibit l-leucine uptake was far more efficient than bch. likewise,jph203 and bch inhibited yd-38 cell growth,with jph203 being superior to bch. jph203 up-regulated the population of apoptotic yd-38 cells through the activation of apoptotic factors,including caspases and parp. these results suggest that the inhibition of l-type amino acid transporter 1 activity via jph203,which may act as a potential novel anti-oral-cancer agent,leads to apoptosis by inducing the intracellular depletion of the neutral amino acids essential for cancer cell growth in yd-38 human oral cancer cells. © 2014 the japanese pharmacological society.