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.
Oral Biology Research Institute, Chosun University School of Dentistry, Korea.
Dae-Woong
DW
Yun
Seul Ah
SA
Lee
Min-Gyeong
MG
Park
Jae-Sung
JS
Kim
Sun-Kyoung
SK
Yu
Mi-Ra
MR
Park
Su-Gwan
SG
Kim
Ji-Su
JS
Oh
Chun Sung
CS
Kim
Heung-Joong
HJ
Kim
Jin-Soo
JS
Kim
Hong Sung
HS
Chun
Yoshikatsu
Y
Kanai
Hitoshi
H
Endou
Michael F
MF
Wempe
Do Kyung
DK
Kim
D027062:Amino Acid Transport System L / Q000037:antagonists & inhibitors*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001583:Benzoxazoles / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000378:metabolism; D006801:Humans; D027283:Large Neutral Amino Acid-Transporter 1 / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
C548172:2-amino-3-(4-((5-amino-2-phenylbenzo(d)oxazol-7-yl)methoxy)-3,5-dichlorophenyl)propanoic acid; D027062:Amino Acid Transport System L; D000970:Antineoplastic Agents; D001583:Benzoxazoles; D027282:Fusion Regulatory Protein 1, Heavy Chain; D027283:Large Neutral Amino Acid-Transporter 1; D014443:Tyrosine; D020169:Caspases; D007930:Leucine