Inhibition of L-type amino acid transporter modulates the expression of cell cycle regulatory factors in KB oral cancer cells.
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.
Kim
Chun Sung
CS
Department of Oralbiochemistry, Chosun University School of Dentistry, Dong-gu, Gwangju 501-759, Korea.
Moon
In-Sung
IS
Park
Ju-Hyun
JH
Shin
Woo-Cheol
WC
Chun
Hong Sung
HS
Lee
Sook-Young
SY
Kook
Joong-Ki
JK
Kim
Heung-Joong
HJ
Park
Joo-Cheol
JC
Endou
Hitoshi
H
Kanai
Yoshikatsu
Y
Lee
Byung-Kwon
BK
Kim
Do Kyung
DK
D026905:Amino Acid Transport Systems / Q000037:antagonists & inhibitors*; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D006801:Humans; D047468:Immunoprecipitation; D009062:Mouth Neoplasms / Q000473:pathology*
D026905:Amino Acid Transport Systems; D018797:Cell Cycle Proteins