1.Inhibition of histone-deacetylase activity by short-chain fatty acids and some polyphenol metabolites formed in the colon.
Waldecker M1, Kautenburger T, Daumann H, Busch C, Schrenk D. J Nutr Biochem. 2008 Sep;19(9):587-93. Epub 2007 Dec 3.
Colorectal cancer is the most abundant cause of cancer mortality in the Western world. Nutrition and the microbial flora are considered to have a marked influence on the risk of colorectal cancer, the formation of butyrate and other short-chain fatty acids (SCFAs) possibly playing a major role as chemopreventive products of microbial fermentation in the colon. In this study, we investigated the effects of butyrate, other SCFAs, and of a number of phenolic SCFA and trans-cinnamic acid derivatives formed during the intestinal degradation of polyphenolic constituents of fruits and vegetables on global histone deacetylase (HDAC) activity in nuclear extracts from colon carcinoma cell cultures using tert-butoxycarbonyl-lysine (acetylated)-4-amino-7-methylcoumarin (Boc-Lys(Ac)-AMC) as substrate. Inhibition of HDAC activity, e.g., by butyrate, is related to a suppression of malignant transformation and a stimulation of apoptosis of precancerous colonic cells.
2.Evaluation of the pharmacodynamic effects of MGCD0103 from preclinical models to human using a novel HDAC enzyme assay.
Bonfils C1, Kalita A, Dubay M, Siu LL, Carducci MA, Reid G, Martell RE, Besterman JM, Li Z. Clin Cancer Res. 2008 Jun 1;14(11):3441-9. doi: 10.1158/1078-0432.CCR-07-4427.
PURPOSE: The pharmacodynamic properties of MGCD0103, an isotype-selective inhibitor of histone deacetylase (HDAC), were evaluated in preclinical models and patients with a novel whole-cell HDAC enzyme assay.
