TitleDietary agents as histone deacetylase inhibitors.
Publication TypeJournal Article
Year of Publication2006
AuthorsMyzak MC, Ho E, Dashwood RH
JournalMol Carcinog
Volume45
Issue6
Pagination443-6
Date Published2006 Jun
ISSN0899-1987
KeywordsDiet, Enzyme Inhibitors, Histone Deacetylase Inhibitors, Humans
Abstract

In cancer cells, an imbalance often exists between histone acetyltransferase (HAT) and histone deacetylase (HDAC) activities, and various drug companies are actively seeking competitive HDAC inhibitors for chemotherapeutic intervention. Cancer cells appear to be more sensitive than nontransformed cells to HDAC inhibitors, which disrupt the cell cycle and induce apoptosis via derepression of genes such as P21 and BAX. However, in the search for potent HDAC inhibitors with cancer therapeutic potential, a tendency exists to overlook or dismiss weak ligands that could prove effective in cancer prevention. Butyrate, diallyl disulfide (DADS), and sulforaphane (SFN) are three dietary agents that exhibit HDAC inhibitory activity in vitro and/or in vivo, and other such dietary agents probably will be discovered that affect HDAC activity. We make the distinction between 'pharmacologic' agents that potently derepress gene expression, during therapeutic intervention, and dietary HDAC inhibitors that, as weak ligands, might subtly regulate the expression of genes involved in cell growth and apoptosis. An important issue for future study is to determine the extent to which dietary HDAC inhibitors, by modulating genes such as p21 and Bax, enable normal, nontransformed cells to respond most effectively to external stimuli and toxic insults.

DOI10.1002/mc.20224
Alternate JournalMol. Carcinog.
PubMed ID16652377
PubMed Central IDPMC2267873
Grant ListP01 CA090890 / CA / NCI NIH HHS / United States
P01 CA090890-01A20003 / CA / NCI NIH HHS / United States
R01 CA080176 / CA / NCI NIH HHS / United States
CA90890 / CA / NCI NIH HHS / United States
CA80176 / CA / NCI NIH HHS / United States
R29 CA065525 / CA / NCI NIH HHS / United States
P01 CA090890-05 / CA / NCI NIH HHS / United States
R01 CA065525 / CA / NCI NIH HHS / United States
R01 CA065525-08 / CA / NCI NIH HHS / United States
R01 CA065525-09 / CA / NCI NIH HHS / United States
R01 CA080176-05 / CA / NCI NIH HHS / United States
CA65525 / CA / NCI NIH HHS / United States
P01 CA090890-01A29001 / CA / NCI NIH HHS / United States