Different Response Profiles of Gastrointestinal Cancer Cells to an L-Type Amino Acid Transporter Inhibitor, JPH203.

Abstract

BACKGROUND/AIM:

L-type amino acid transporter 1 (LAT1) is a promising molecular target for cancer therapy. The present study aimed to characterize the anti-cancer effects of JPH203, an LAT1-selective inhibitor, on gastrointestinal cancer cells.

MATERIALS AND METHODS:

Three esophageal, two gastric, and two colon cancer cell lines were used. Cytotoxic effects of JPH203 were assessed by a WST-8 assay. LAT1 mRNA levels were determined by quantitative PCR. The inhibitory property of JPH203 against LAT1 function was examined by a transport assay.

RESULTS:

JPH203 treatment significantly reduced the viability of all gastric and colon cancer cells. While LAT1 expression levels and inhibitory potencies of JPH203 on LAT1 functions were comparable among the cells, all the esophageal cells were resistant to JPH203.

CONCLUSION:

JPH203 was effective in reducing gastric and colon cancer cells. To clarify its cell type-dependent efficacy, identification of the causal factors for JPH203 resistance will be needed.

• Authors: Yasuhide Muto, Tomomi Furihata, Meika Kaneko, Kosuke Higuchi, Kentaro Okunushi, Hanae Morio, Yoshie Reien, Masaya Uesato, Hisahiro Matsubara, Naohiko Anzai
• Journal: Anticancer research (Anticancer Res) Vol. 39 Issue 1 Pg. 159-165 (Jan 2019) ISSN: 1791-7530 [Electronic] Greece
• PMID: 30591453 (Publication Type: Journal Article)
• Copyright: Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• 2-amino-3-(4-((5-amino-2-phenylbenzo(d)oxazol-7-yl)methoxy)-3,5-dichlorophenyl)propanoic acid
• Benzoxazoles
• Large Neutral Amino Acid-Transporter 1
• Tyrosine

Topics

• Apoptosis (drug effects)
• Benzoxazoles (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colonic Neoplasms (drug therapy, genetics, pathology)
• Gastrointestinal Neoplasms (drug therapy, genetics, pathology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Large Neutral Amino Acid-Transporter 1 (genetics)
• Tyrosine (analogs & derivatives, pharmacology)