JPH203, an L-Type Amino Acid Transporter 1–Selective Compound, Induces Apoptosis of YD-38 Human Oral Cancer Cells

• Main Authors: Dae-Woong Yun, Seul Ah Lee, Min-Gyeong Park, Jae-Sung Kim, Sun-Kyoung Yu, Mi-Ra Park, Su-Gwan Kim, Ji-Su Oh, Chun Sung Kim, Heung-Joong Kim, Jin-Soo Kim, Hong Sung Chun, Yoshikatsu Kanai, Hitoshi Endou, Michael F. Wempe, Do Kyung Kim
• Format: Article
• Language: English
• Published: Elsevier 2014-01-01
• Series: Journal of Pharmacological Sciences
• Online Access: http://www.sciencedirect.com/science/article/pii/S134786131930204X

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. Keywords:: JPH203, L-type amino acid transporter 1, apoptosis, oral cancer cell, anti-cancer therapy