Over-expression of Adenine Nucleotide Translocase 1 (ANT1) Induces Apoptosis and Tumor Regression <it>in vivo</it>

<p>Abstract</p> <p>Background</p> <p>Adenine nucleotide translocase (ANT) is located in the inner mitochondrial membrane and catalyzes the exchange of mitochondrial ATP for cytosolic ADP. ANT has been known to be a major component of the permeability transition pore com...

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Main Authors: Kim Chul-Woo, Aung Khin, Jeon Yoon-Kyung, Choi Yun, Jang Ji-Young
Format: Article
Language:English
Published: BMC 2008-06-01
Series:BMC Cancer
Online Access:http://www.biomedcentral.com/1471-2407/8/160
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author Kim Chul-Woo
Aung Khin
Jeon Yoon-Kyung
Choi Yun
Jang Ji-Young
author_facet Kim Chul-Woo
Aung Khin
Jeon Yoon-Kyung
Choi Yun
Jang Ji-Young
author_sort Kim Chul-Woo
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Adenine nucleotide translocase (ANT) is located in the inner mitochondrial membrane and catalyzes the exchange of mitochondrial ATP for cytosolic ADP. ANT has been known to be a major component of the permeability transition pore complex of mitochondria and contributes to mitochondria-mediated apoptosis. Human ANT has four isoforms (ANT1, ANT2, ANT3, and ANT4), and the expression of the ANT isoforms is variable depending on the tissue and cell type, developmental stage, and proliferation status. Among the isoforms, ANT1 is highly expressed in terminally-differentiated tissues, but expressed in low levels in proliferating cells, such as cancer cells. In particular, over-expression of ANT1 induces apoptosis in cultured tumor cells.</p> <p>Methods</p> <p>We applied an ANT1 gene transfer approach to induce apoptosis and to evaluate the anti-tumor effect of ANT1 in a nude mouse model.</p> <p>Results</p> <p>We demonstrated that ANT1 transfection induced apoptosis of MDA-MB-231 cells, inactivated NF-κB activity, and increased Bax expression. ANT1-inducing apoptosis was accompanied by the disruption of mitochondrial membrane potential, cytochrome c release and the activation of caspases-9 and -3. Moreover, ANT1 transfection significantly suppressed tumor growth <it>in vivo</it>.</p> <p>Conclusion</p> <p>Our results suggest that ANT1 transfection may be a useful therapeutic modality for the treatment of cancer.</p>
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spelling doaj.art-225bed89652342b5ba6b21d7a2b357232022-12-22T03:05:01ZengBMCBMC Cancer1471-24072008-06-018116010.1186/1471-2407-8-160Over-expression of Adenine Nucleotide Translocase 1 (ANT1) Induces Apoptosis and Tumor Regression <it>in vivo</it>Kim Chul-WooAung KhinJeon Yoon-KyungChoi YunJang Ji-Young<p>Abstract</p> <p>Background</p> <p>Adenine nucleotide translocase (ANT) is located in the inner mitochondrial membrane and catalyzes the exchange of mitochondrial ATP for cytosolic ADP. ANT has been known to be a major component of the permeability transition pore complex of mitochondria and contributes to mitochondria-mediated apoptosis. Human ANT has four isoforms (ANT1, ANT2, ANT3, and ANT4), and the expression of the ANT isoforms is variable depending on the tissue and cell type, developmental stage, and proliferation status. Among the isoforms, ANT1 is highly expressed in terminally-differentiated tissues, but expressed in low levels in proliferating cells, such as cancer cells. In particular, over-expression of ANT1 induces apoptosis in cultured tumor cells.</p> <p>Methods</p> <p>We applied an ANT1 gene transfer approach to induce apoptosis and to evaluate the anti-tumor effect of ANT1 in a nude mouse model.</p> <p>Results</p> <p>We demonstrated that ANT1 transfection induced apoptosis of MDA-MB-231 cells, inactivated NF-κB activity, and increased Bax expression. ANT1-inducing apoptosis was accompanied by the disruption of mitochondrial membrane potential, cytochrome c release and the activation of caspases-9 and -3. Moreover, ANT1 transfection significantly suppressed tumor growth <it>in vivo</it>.</p> <p>Conclusion</p> <p>Our results suggest that ANT1 transfection may be a useful therapeutic modality for the treatment of cancer.</p>http://www.biomedcentral.com/1471-2407/8/160
spellingShingle Kim Chul-Woo
Aung Khin
Jeon Yoon-Kyung
Choi Yun
Jang Ji-Young
Over-expression of Adenine Nucleotide Translocase 1 (ANT1) Induces Apoptosis and Tumor Regression <it>in vivo</it>
BMC Cancer
title Over-expression of Adenine Nucleotide Translocase 1 (ANT1) Induces Apoptosis and Tumor Regression <it>in vivo</it>
title_full Over-expression of Adenine Nucleotide Translocase 1 (ANT1) Induces Apoptosis and Tumor Regression <it>in vivo</it>
title_fullStr Over-expression of Adenine Nucleotide Translocase 1 (ANT1) Induces Apoptosis and Tumor Regression <it>in vivo</it>
title_full_unstemmed Over-expression of Adenine Nucleotide Translocase 1 (ANT1) Induces Apoptosis and Tumor Regression <it>in vivo</it>
title_short Over-expression of Adenine Nucleotide Translocase 1 (ANT1) Induces Apoptosis and Tumor Regression <it>in vivo</it>
title_sort over expression of adenine nucleotide translocase 1 ant1 induces apoptosis and tumor regression it in vivo it
url http://www.biomedcentral.com/1471-2407/8/160
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