Journal
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
Volume 46, Issue 3, Pages 181-199Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/10409238.2011.557713
Keywords
Epigenetics; chromatin remodeling; protein acetylation; HDAC; chemoprevention; chemoprotection; cancer
Categories
Funding
- NIH [CA90890, CA65525, CA122906, CA122959, CA80176]
- NIEHS [P30 ES00210]
Ask authors/readers for more resources
There is growing interest in the epigenetic mechanisms that are dysregulated in cancer and other human pathologies. Under this broad umbrella, modulators of histone deacetylase (HDAC) activity have gained interest as both cancer chemopreventive and therapeutic agents. Of the first generation, FDA-approved HDAC inhibitors to have progressed to clinical trials, vorinostat represents a direct acting compound with structural features suitable for docking into the HDAC pocket, whereas romidepsin can be considered a prodrug that undergoes reductive metabolism to generate the active intermediate (a zinc-binding thiol). It is now evident that other agents, including those in the human diet, can be converted by metabolism to intermediates that affect HDAC activity. Examples are cited of short-chain fatty acids, seleno-a-keto acids, small molecule thiols, mercapturic acid metabolites, indoles, and polyphenols. The findings are discussed in the context of putative endogenous HDAC inhibitors generated by intermediary metabolism (e. g. pyruvate), the yin-yang of HDAC inhibition versus HDAC activation, and the screening assays that might be most appropriate for discovery of novel HDAC inhibitors in the future.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available