Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
ISSN-L : 1347-8613
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JPH203, an L-Type Amino Acid Transporter 1–Selective Compound, Induces Apoptosis of YD-38 Human Oral Cancer Cells
Dae-Woong YunSeul Ah LeeMin-Gyeong ParkJae-Sung KimSun-Kyoung YuMi-Ra ParkSu-Gwan KimJi-Su OhChun Sung KimHeung-Joong KimJin-Soo KimHong Sung ChunYoshikatsu KanaiHitoshi EndouMichael F. WempeDo Kyung Kim
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2014 Volume 124 Issue 2 Pages 208-217


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.

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© 2014 The Japanese Pharmacological Society
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