BCH, an Inhibitor of System L Amino Acid Transporters, Induces Apoptosis in Cancer Cells(Molecular and Cell Biology)
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概要
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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.
- 公益社団法人日本薬学会の論文
- 2008-06-01
著者
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KIM Do
Department of Aqualife Medicine, College of Fisheries and Ocean Sciences, Chonnam National Universit
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Endou Hitoshi
Department of Pharmacology and Toxicology, Kyorin University School of Medicine
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Kim Do
杏林大学 医学部薬理学
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Kim Do-kyung
Department Of Pharmacology And Toxicology Kyorin University School Of Medicine
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KANAI Yoshikatsu
Department of Pharmacology and Toxicology, Kyorin University School of Medicine
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Endou Hitoshi
群馬大学 医学系研究科病態制御内科学
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Endou Hitoshi
杏林大学 医学部薬理学教室
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Kim Chun
Oral Biology Research Institute And The Second Stage Of Bk21 Chosun University College Of Dentistry
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Chun Hong
Department Of Biotechnology (bk21 Program) Chosun University:research Center For Proteineous Materia
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Cha Seok
Department Of Oral Physiology And The Second Stage Of Bk21 Chosun University College Of Dentistry
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Endou H
Kyorin Univ. School Of Medicine Tokyo Jpn
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Kim Chun
Department of Oralbiochemistry, Chosun University School of Dentistry
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Lee Sook-Young
Research Center for Oral Disease Regulation of the Aged, Chosun University School of Dentistry
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Kanai Yoshikatsu
Department Of Pharmacology & Toxicology Kyorin University School Of Medicine
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Kanai Yoshikatsu
Department Of Pharmacol. Toxicol. Kyorin Univ.
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Endou Hitoshi
Department Of Pharmacology & Toxicology Kyorin University School Of Medicine
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CHO Seon-Ho
Department of Oral Physiology and The Second Stage of BK21, Chosun University College of Dentistry
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Kim Do
Department Of Pharmacology And Toxicology Kyorin University School Of Medicine
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Do Kyung
Department Of Pharmacology And Toxicology Kyorin University School Of Medicine
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Kim Do
Department Of Aqualife Medicine College Of Fisheries And Ocean Sciences Chonnam National University
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Lee Sook-young
Research Center For Proteineous Materials Chosun University
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Kanai Yoshikatsu
Division Of Bio-system Pharmacology Department Of Pharmacology Osaka University Graduate School Of M
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Kim Do
Department Of Applied Mathematics Pukyong National University
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Kim Do
Department Of Applied Mathematics College Of Natural Sciences National Fisheries University Of Pusan
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