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

DOI Web Site Web Site PubMed 被引用文献12件 参考文献30件
  • Yun Dae-Woong
    Oral Biology Research Institute, Chosun University School of Dentistry, Korea
  • Lee Seul Ah
    Oral Biology Research Institute, Chosun University School of Dentistry, Korea
  • Park Min-Gyeong
    Oral Biology Research Institute, Chosun University School of Dentistry, Korea
  • Kim Jae-Sung
    Oral Biology Research Institute, Chosun University School of Dentistry, Korea Regional Innovation Center for Dental Science & Engineering, Chosun University School of Dentistry, Korea
  • Yu Sun-Kyoung
    Oral Biology Research Institute, Chosun University School of Dentistry, Korea
  • Park Mi-Ra
    Oral Biology Research Institute, Chosun University School of Dentistry, Korea
  • Kim Su-Gwan
    Oral Biology Research Institute, Chosun University School of Dentistry, Korea Regional Innovation Center for Dental Science & Engineering, Chosun University School of Dentistry, Korea
  • Oh Ji-Su
    Oral Biology Research Institute, Chosun University School of Dentistry, Korea Regional Innovation Center for Dental Science & Engineering, Chosun University School of Dentistry, Korea
  • Kim Chun Sung
    Oral Biology Research Institute, Chosun University School of Dentistry, Korea
  • Kim Heung-Joong
    Oral Biology Research Institute, Chosun University School of Dentistry, Korea
  • Kim Jin-Soo
    Oral Biology Research Institute, Chosun University School of Dentistry, Korea
  • Chun Hong Sung
    Department of Biotechnology, Chosun University School of Dentistry, Korea
  • Kanai Yoshikatsu
    Department of Pharmacology, Osaka University Graduate School of Medicine, Japan
  • Endou Hitoshi
    Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Japan J-Pharma Co., Ltd., Japan
  • Wempe Michael F.
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver Anschutz Medical Campus, USA
  • Kim Do Kyung
    Oral Biology Research Institute, Chosun University School of Dentistry, Korea Regional Innovation Center for Dental Science & Engineering, Chosun University School of Dentistry, Korea

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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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