Polyamines pp 475-491 | Cite as

Use of Polyamine Derivatives as Selective Histone Deacetylase Inhibitors

  • Patrick M. Woster
Part of the Methods in Molecular Biology book series (MIMB, volume 720)


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.

Key words

Histone deacetylase Polyaminohydroxamic acid Polyaminobenzamide Annexin A1 Polyamine transport Breast cancer 


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Patrick M. Woster
    • 1
  1. 1.Department of Pharmaceutical SciencesWayne State UniversityDetroitUSA

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