Inhibition of L-Type Amino Acid Transporter Modulates the Expression of Cell Cycle Regulatory Factors in KB Oral Cancer Cells

Chun Sung Kim; In-Sung Moon; Ju-Hyun Park; Woo-Cheol Shin; Hong Sung Chun; Sook-Young Lee; Joong-Ki Kook; Heung-Joong Kim; Joo-Cheol Park; Hitoshi Endou; Yoshikatsu Kanai; Byung-Kwon Lee; Do Kyung Kim

doi:10.1248/bpb.33.1117

Regular Articles

Inhibition of L-Type Amino Acid Transporter Modulates the Expression of Cell Cycle Regulatory Factors in KB Oral Cancer Cells

Chun Sung Kim, In-Sung Moon, Ju-Hyun Park, Woo-Cheol Shin, Hong Sung Chun, Sook-Young Lee, Joong-Ki Kook, Heung-Joong Kim, Joo-Cheol Park, Hitoshi Endou, Yoshikatsu Kanai, Byung-Kwon Lee, Do Kyung Kim

Author information

Chun Sung Kim
Department of Oralbiochemistry, Chosun University School of Dentistry
In-Sung Moon
Oral Biology Research Institute, Chosun University School of Dentistry
Ju-Hyun Park
Oral Biology Research Institute, Chosun University School of Dentistry
Woo-Cheol Shin
Oral Biology Research Institute, Chosun University School of Dentistry
Hong Sung Chun
Department of Biotechnology (BK21 Program), Chosun University
Sook-Young Lee
Research Center for Oral Disease Regulation of the Aged, Chosun University School of Dentistry
Joong-Ki Kook
Department of Oralbiochemistry, Chosun University School of Dentistry
Heung-Joong Kim
Oral Biology Research Institute, Chosun University School of Dentistry
Joo-Cheol Park
Department of Oral Histology and Developmental Biology, Seoul National University School of Dentistry
Hitoshi Endou
Department of Pharmacology and Toxicology, Kyorin University School of Medicine
Yoshikatsu Kanai
Department of Pharmacology, Osaka University Graduate School of Medicine
Byung-Kwon Lee
Department of Microbiology, University of Tennessee
Do Kyung Kim
Oral Biology Research Institute, Chosun University School of Dentistry

Keywords: L-type amino acid transporter, cancer cell, cell cycle regulatory factor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid

JOURNAL FREE ACCESS

2010 Volume 33 Issue 7 Pages 1117-1121

DOI https://doi.org/10.1248/bpb.33.1117

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Abstract

The purpose of this study was to examine the effect of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), an inhibitor of L-type amino acid transporters, on the cell growth suppression in KB human oral cancer cells and to study the roles of cell cycle regulatory factors in the BCH-induced growth inhibition. The effect of BCH on cell growth suppression and the influence of BCH to cell cycle regulatory factors in KB cell growth inhibition were examined using cell cycle analysis, immunoblotting and immunoprecipitation. The BCH treatment induced cell cycle arrest at G1 phase in KB cells. The expression of cyclin D3 was remarkably decreased by BCH treatment. The BCH inhibited the expression of cyclin-dependent protein kinase 6 (CDK6) in a time-dependent manner. In addition, the expression of CDK inhibitor p27 was increased by BCH treatment in KB cells, but not CDK inhibitors p21 and p15. These results suggest that, in KB cells, the inhibition of LAT1 by BCH causes cell cycle arrest at G1 phase by inhibiting cyclin D3–CDK6 complex whereas increasing expression of a CDK inhibitor p27.

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