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

Journal of Pharmacological Sciences

Mi-Ra Park¹  Michael F. Wempe³  Sun-Kyoung Yu¹  Jae-Sung Kim¹  Hong Sung Chun⁵  Min-Gyeong Park¹  Hitoshi Endou²  Seul Ah Lee¹  Yoshikatsu Kanai⁴  Su-Gwan Kim¹  Chun Sung Kim¹  Do Kyung Kim¹  Dae-Woong Yun¹  Jin-Soo Kim¹  Heung-Joong Kim¹  Ji-Su Oh¹ 

[1] Oral Biology Research Institute, Chosun University School of Dentistry, Korea;Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Japan;Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver Anschutz Medical Campus, USA;Department of Pharmacology, Osaka University Graduate School of Medicine, Japan;Department of Biotechnology, Chosun University School of Dentistry, Korea

关键词: JPH203;    L-type amino acid transporter 1;    apoptosis;    oral cancer cell;    anti-cancer therapy;   

DOI  :  10.1254/jphs.13154FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(36)Cited-By(9)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.

【 授权许可】

Unknown