The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin Journal Article
| Authors: | Butler, L. M.; Zhou, X.; Xu, W. S.; Scher, H. I.; Rifkind, R. A.; Marks, P. A.; Richon, V. M. |
| Article Title: | The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin |
| Abstract: | 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. |
| Keywords: | controlled study; human tissue; unclassified drug; human cell; promoter region; histone deacetylase inhibitor; cancer growth; neoplasms; cell division; apoptosis; enzyme inhibition; gene expression; down-regulation; cell differentiation; tumor cells, cultured; cloning, molecular; cancer inhibition; molecular sequence data; genetic transfection; cell culture; messenger rna; enzyme inhibitors; rna, messenger; cell transformation; colon tumor; vitamin d; nucleotide sequence; breast tumor; carrier proteins; vorinostat; hydroxamic acids; base sequence; binding protein; binding site; down regulation; gene induction; dna primers; up-regulation; histone deacetylases; gene construct; thioredoxin; humans; human; priority journal; article; thioredoxin binding protein 2 |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 99 |
| Issue: | 18 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2002-09-03 |
| Start Page: | 11700 |
| End Page: | 11705 |
| Language: | English |
| DOI: | 10.1073/pnas.182372299 |
| PUBMED: | 12189205 |
| PROVIDER: | scopus |
| PMCID: | PMC129332 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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