PMID- 18520037
OWN - NLM
STAT- MEDLINE
DCOM- 20080630
LR  - 20190720
IS  - 0918-6158 (Print)
IS  - 0918-6158 (Linking)
VI  - 31
IP  - 6
DP  - 2008 Jun
TI  - BCH, an inhibitor of system L amino acid transporters, induces apoptosis in 
      cancer cells.
PG  - 1096-100
AB  - PURPOSE: L-Type amino acid transporter 1 (LAT1) is highly expressed in cancer 
      cells to support their continuous growth and proliferation. We have examined the 
      effect of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), an inhibitor of 
      system L amino acid transporters, and the mechanism by which BCH suppresses cell 
      growth in cancer cells. METHODS: The effect of BCH and the mechanism of BCH on 
      cell growth suppression in cancer cells were examined using amino acid transport 
      measurement, MTT assay, DNA fragmentation analysis, terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) assay and immunoblotting. 
      RESULTS: BCH inhibited L-leucine transport in a concentration-dependent manner, 
      and it inhibited cell growth in a time-dependent manner in KB human oral 
      epidermoid carcinoma cells, Saos2 human osteogenic sarcoma cells and C6 rat 
      glioma cells. The formation of a DNA ladder was observed, and the number of 
      TUNEL-positive cells was increased with BCH treatment. Furthermore, the 
      proteolytic processing of caspase-3 in KB and C6 cells and of caspase-7 in KB, 
      Saos2 and C6 cells was increased by BCH treatment. CONCLUSION: These results 
      suggest that the inhibition of LAT1 activity by BCH leads to apoptotic cancer 
      cell death by inducing intracellular depletion of neutral amino acids necessary 
      for cancer cell growth.
FAU - Kim, Chun Sung
AU  - Kim CS
AD  - Department of Oral Physiology and The Second Stage of BK21, Chosun University 
      College of Dentistry, Seosuk-dong, Gwangju, Korea.
FAU - Cho, Seon-Ho
AU  - Cho SH
FAU - Chun, Hong Sung
AU  - Chun HS
FAU - Lee, Sook-Young
AU  - Lee SY
FAU - Endou, Hitoshi
AU  - Endou H
FAU - Kanai, Yoshikatsu
AU  - Kanai Y
FAU - Kim, Do Kyung
AU  - Kim DK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Actins)
RN  - 0 (Amino Acid Transport Systems)
RN  - 0 (Amino Acids, Cyclic)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Large Neutral Amino Acid-Transporter 1)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (Thiazoles)
RN  - 20448-79-7 (2-aminobicyclo(2,2,1)heptane-2-carboxylic acid)
RN  - EC 3.4.22.- (Caspases)
RN  - EUY85H477I (thiazolyl blue)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - Actins/biosynthesis/genetics
MH  - Amino Acid Transport Systems/*antagonists & inhibitors
MH  - Amino Acids, Cyclic/*pharmacology
MH  - *Antineoplastic Agents
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Caspases/metabolism
MH  - Cell Division/drug effects
MH  - Cell Line, Tumor
MH  - DNA Fragmentation
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - KB Cells
MH  - Large Neutral Amino Acid-Transporter 1/genetics/metabolism
MH  - Leucine/metabolism
MH  - Tetrazolium Salts
MH  - Thiazoles
EDAT- 2008/06/04 09:00
MHDA- 2008/07/01 09:00
CRDT- 2008/06/04 09:00
PHST- 2008/06/04 09:00 [pubmed]
PHST- 2008/07/01 09:00 [medline]
PHST- 2008/06/04 09:00 [entrez]
AID - JST.JSTAGE/bpb/31.1096 [pii]
AID - 10.1248/bpb.31.1096 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2008 Jun;31(6):1096-100. doi: 10.1248/bpb.31.1096.