Premium
Dietary agents as histone deacetylase inhibitors
Author(s) -
Myzak Melinda C.,
Ho Emily,
Dashwood Roderick H.
Publication year - 2006
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20224
Subject(s) - histone deacetylase , biology , histone deacetylase 5 , sulforaphane , histone acetyltransferase , hdac11 , cancer cell , epigenetics , histone , cancer research , histone deacetylase 2 , apoptosis , microbiology and biotechnology , cancer , pharmacology , gene , biochemistry , genetics
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. © 2006 Wiley‐Liss, Inc.