The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin

Suberoylanilide hydroxamic acid (SAHA) is a potent inhibitor of histone deacetylases (HDACs) that causes growth arrest, differentiation, and/or apoptosis of many tumor types in vitro and in vivo. SAHA is in clinical trials for the treatment of cancer. HDAC inhibitors induce the expression of less th...

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التفاصيل البيبلوغرافية
المؤلفون الرئيسيون: Butler, Lisa M., Zhou, Xianbo, Xu, Wei-Sheng, Scher, Howard I., Rifkind, Richard A., Marks, Paul A., Richon, Victoria M.
التنسيق: مقال
اللغة:en
منشور في: The National Academy of Sciences 2002
الموضوعات:
Biological Sciences
الوصول للمادة أونلاين:https://ncbi.nlm.nih.gov/pmc/articles/PMC129332/
https://ncbi.nlm.nih.gov/pubmed/12189205
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1073/pnas.182372299
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spelling pubmed-1293322003-03-03 The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin Butler, Lisa M. Zhou, Xianbo Xu, Wei-Sheng Scher, Howard I. Rifkind, Richard A. Marks, Paul A. Richon, Victoria M. Proc Natl Acad Sci U S A Biological Sciences Suberoylanilide hydroxamic acid (SAHA) is a potent inhibitor of histone deacetylases (HDACs) that causes growth arrest, differentiation, and/or apoptosis of many tumor types in vitro and in vivo. SAHA is in clinical trials for the treatment of cancer. HDAC inhibitors induce the expression of less than 2% of genes in cultured cells. In this study we show that SAHA induces the expression of vitamin D-up-regulated protein 1/thioredoxin-binding protein-2 (TBP-2) in transformed cells. As the expression of TBP-2 mRNA is increased, the expression of a second gene, thioredoxin, is decreased. In transient transfection assays, HDAC inhibitors induce TBP-2 promoter constructs, and this induction requires an NF-Y binding site. We report here that TBP-2 expression is reduced in human primary breast and colon tumors compared with adjacent tissue. These results support a model in which the expression of a subset of genes (i.e., including TBP-2) is repressed in transformed cells, leading to a block in differentiation, and culture of transformed cells with SAHA causes re-expression of these genes, leading to induction of growth arrest, differentiation, and/or apoptosis. The National Academy of Sciences 2002-09-03 2002-08-20 /pmc/articles/PMC129332/ /pubmed/12189205 http://dx.doi.org/10.1073/pnas.182372299 Text en Copyright © 2002, The National Academy of Sciences
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Biological Sciences
spellingShingle Biological Sciences
Butler, Lisa M.
Zhou, Xianbo
Xu, Wei-Sheng
Scher, Howard I.
Rifkind, Richard A.
Marks, Paul A.
Richon, Victoria M.
The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin
description Suberoylanilide hydroxamic acid (SAHA) is a potent inhibitor of histone deacetylases (HDACs) that causes growth arrest, differentiation, and/or apoptosis of many tumor types in vitro and in vivo. SAHA is in clinical trials for the treatment of cancer. HDAC inhibitors induce the expression of less than 2% of genes in cultured cells. In this study we show that SAHA induces the expression of vitamin D-up-regulated protein 1/thioredoxin-binding protein-2 (TBP-2) in transformed cells. As the expression of TBP-2 mRNA is increased, the expression of a second gene, thioredoxin, is decreased. In transient transfection assays, HDAC inhibitors induce TBP-2 promoter constructs, and this induction requires an NF-Y binding site. We report here that TBP-2 expression is reduced in human primary breast and colon tumors compared with adjacent tissue. These results support a model in which the expression of a subset of genes (i.e., including TBP-2) is repressed in transformed cells, leading to a block in differentiation, and culture of transformed cells with SAHA causes re-expression of these genes, leading to induction of growth arrest, differentiation, and/or apoptosis.
author Butler, Lisa M.
Zhou, Xianbo
Xu, Wei-Sheng
Scher, Howard I.
Rifkind, Richard A.
Marks, Paul A.
Richon, Victoria M.
author_facet Butler, Lisa M.
Zhou, Xianbo
Xu, Wei-Sheng
Scher, Howard I.
Rifkind, Richard A.
Marks, Paul A.
Richon, Victoria M.
author_sort Butler, Lisa M.
title The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin
title_short The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin
title_full The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin
title_fullStr The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin
title_full_unstemmed The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin
title_sort histone deacetylase inhibitor saha arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin
publisher The National Academy of Sciences
publisher_facet The National Academy of Sciences
publishDate 2002
url https://ncbi.nlm.nih.gov/pmc/articles/PMC129332/
https://ncbi.nlm.nih.gov/pubmed/12189205
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1073/pnas.182372299
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