Authors: Myzak, Melinda C.; Dashwood, Roderick H.

Source: Current Drug Targets, Volume 7, Number 4, April 2006 , pp. 443-452(10)

Publisher: Bentham Science Publishers

Abstract:

Cancer is a multi-factorial process involving genetic and epigenetic events which result in neoplastic transformation. Reversal of aberrant epigenetic events, including those that modulate the transcriptional activity of genes associated with various signaling pathways, holds the prospect of influencing multiple stages of tumorigenesis. Perturbation of normal histone acetylation status can result in undesirable phenotypic changes, including developmental disorders and cancer. Indeed, aberrant histone acetylation may be an etiological factor in several, if not all, types of cancer. In general, histone acetylation leads to chromatin remodeling and a de-repression of transcription. Histone deacetylase (HDAC) inhibitors may be useful for cancer prevention and therapy by virtue of their ability to 'reactivate' the expression of epigenetically silenced genes, including those involved in differentiation, cell cycle regulation, apoptosis, angiogenesis, invasion, and metastasis. Several natural and synthetic HDAC inhibitors have been shown to affect the growth and survival of tumor cells in vitro and in vivo. Interestingly, three dietary chemopreventive agents, butyrate, diallyl disulfide, and sulforaphane, also have HDAC inhibitory activity. This review discusses the role of aberrant histone acetylation in tumorigenesis and describes the potential for cancer chemoprevention and therapy with a particular emphasis on dietary HDAC inhibitors.

Keywords: Oncogenic; apoptosis; transcriptional activators; differentiation; chemoprevention

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138945006776359467

Affiliations: 1: Linus Pauling Institute, Weniger 503, Oregon State University, Corvallis, OR 97331-6512, USA.

Publication date: 2006-04-01

More about this publication?

• Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.

Related content

• In this: publication
• By this: publisher
• In this Subject: Pharmacology
• By this author: Myzak, Melinda C. ;  Dashwood, Roderick H.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers