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Use of Polyamine Derivatives as Selective Histone Deacetylase Inhibitors

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Polyamines

Part of the book series: Methods in Molecular Biology ((MIMB,volume 720))

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Abstract

Histone acetylation and deacetylation, mediated by histone acetyltransferase and the 11 isoforms of histone deacetylase, play an important role in gene expression. Histone deacetylase inhibitors have found utility in the treatment of cancer by promoting the reexpression of aberrantly silenced genes that code for tumor suppressor factors. It is unclear which of the 11 histone deacetylase isoforms are important in human cancer. We have designed a series of polyaminohydroxamic acid (PAHA) and polyaminobenzamide (PABA) histone deacetylase inhibitors that exhibit selectivity among four histone deacetylase isoforms. Although all of the active inhibitors promote reexpression of tumor suppressor factors, they produce variable cellular effects ranging from stimulation of growth to cytostasis and cytotoxicity. This chapter describes the procedures used to quantify the global and isoform-specific inhibition caused by these inhibitors, and techniques used to measure cellular effects such as reexpression of tumor suppressor proteins and hyperacetylation of histones H3 and H4. Procedures are also described to examine the ability of PAHAs and PABAs to utilize the polyamine transport system and to induce overexpression of the early apoptotic factor annexin A1.

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Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI, USA

    Patrick M. Woster

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  1. Patrick M. Woster
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Editors and Affiliations

  1. College of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, University Drive 500, Hershey, 17033-0850, Pennsylvania, USA

    Anthony E. Pegg

  2. School of Medicine, Sidney Kimmel Comprehensive, Johns Hopkins University, Orleans St. 1650, Baltimore, 21231, Maryland, USA

    Robert A. Casero, Jr.

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Woster, P.M. (2011). Use of Polyamine Derivatives as Selective Histone Deacetylase Inhibitors. In: Pegg, A., Casero, Jr., R. (eds) Polyamines. Methods in Molecular Biology, vol 720. Humana Press. https://doi.org/10.1007/978-1-61779-034-8_31

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  • DOI: https://doi.org/10.1007/978-1-61779-034-8_31

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-033-1

  • Online ISBN: 978-1-61779-034-8

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