Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556
USA

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Histone Deacetylases as Targets for Dietary Cancer Preventive Agents: Lessons Learned with Butyrate, Diallyl Disulfide, and Sulforaphane

Author(s): Melinda C. Myzak and Roderick H. Dashwood

Affiliation: Linus Pauling Institute, Weniger503, Oregon State University, Corvallis, OR 97331-6512, USA.

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

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Article Details

VOLUME: 7
ISSUE: 4
Page: [443 - 452]
Pages: 10
DOI: 10.2174/138945006776359467
Price: $58