Histone deacetylase inhibitors

can we consider potent anti-neoplastic agents for the treatment of asthma?

Simon G. Royce, Katherine Ververis, Tom C. Karagiannis

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

Histone deacetylase inhibitors have emerged as a new class of anti-cancer therapeutics due to their potent anti-proliferative and apoptotic effects in malignant cells. Accumulating evidence is indicating that histone deacetylase inhibitors may also have potential clinical utility in non-oncological applications, including asthma. However, the potential of histone deacetylase inhibitors in asthma remains controversial. For example, the mechanisms of action of the broad-spectrum histone deacetylase inhibitor, Trichostatin A, in animal models of allergic airways disease are conflicting. Further, there is evidence suggesting potential problems associated with histone deacetylase 2 inhibition and conventional glucocorticosteroid therapy. Similarly, disparate findings are emerging following modulation of the class III, sirtuin 1 enzyme. Indeed, it is becoming apparent that the mechanism of action may not be related to histone deacetylase inhibition activity per se. Further, there is only limited evidence that these compounds possess anti-inflammatory effects in models of asthma. In this review, we provide an overview of the biology of the metal-dependent and sirtuin deacetylases in the context of asthma. The controversies surrounding the potential use of histone deacetylase inhibitors in asthma are discussed and future directions involving the investigation of more specific analogues are explored.
Original languageEnglish
Pages (from-to)338-345
Number of pages8
JournalAnnals of Clinical and Laboratory Science
Volume42
Issue number3
Publication statusPublished - 2012
Externally publishedYes

Keywords

  • asthma
  • allergic airways disease,
  • inflammatory lung condition
  • histone deacetylase inhibitor
  • Trichostatin A

Cite this

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title = "Histone deacetylase inhibitors: can we consider potent anti-neoplastic agents for the treatment of asthma?",
abstract = "Histone deacetylase inhibitors have emerged as a new class of anti-cancer therapeutics due to their potent anti-proliferative and apoptotic effects in malignant cells. Accumulating evidence is indicating that histone deacetylase inhibitors may also have potential clinical utility in non-oncological applications, including asthma. However, the potential of histone deacetylase inhibitors in asthma remains controversial. For example, the mechanisms of action of the broad-spectrum histone deacetylase inhibitor, Trichostatin A, in animal models of allergic airways disease are conflicting. Further, there is evidence suggesting potential problems associated with histone deacetylase 2 inhibition and conventional glucocorticosteroid therapy. Similarly, disparate findings are emerging following modulation of the class III, sirtuin 1 enzyme. Indeed, it is becoming apparent that the mechanism of action may not be related to histone deacetylase inhibition activity per se. Further, there is only limited evidence that these compounds possess anti-inflammatory effects in models of asthma. In this review, we provide an overview of the biology of the metal-dependent and sirtuin deacetylases in the context of asthma. The controversies surrounding the potential use of histone deacetylase inhibitors in asthma are discussed and future directions involving the investigation of more specific analogues are explored.",
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Histone deacetylase inhibitors : can we consider potent anti-neoplastic agents for the treatment of asthma? / Royce, Simon G.; Ververis, Katherine; Karagiannis, Tom C.

In: Annals of Clinical and Laboratory Science, Vol. 42, No. 3, 2012, p. 338-345.

Research output: Contribution to journalArticleResearchpeer-review

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