Cited by 615Histone Deacetylase Inhibitors ResearchGut microbiota and healthEpigenetics and DNA Methylation

Inhibition of histone-deacetylase activity by short-chain fatty acids and some polyphenol metabolites formed in the colon

Waldecker, Markus, Kautenburger, Tanja, Daumann, Heike, Busch, Cordula, Schrenk, Dieter·2008·The Journal of Nutritional Biochemistry

Abstract

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. In nuclear extracts from HT-29 human colon carcinoma cells, butyrate was found to be the most potent HDAC inhibitor (IC50=0.09 mM), while other SCFAs such as propionate were less potent. In the same assay, p-coumaric acid (IC50=0.19 mM), 3-(4-OH-phenyl)-propionate (IC50=0.62 mM) and caffeic acid (IC50=0.85 mM) were the most potent HDAC inhibitors among the polyphenol metabolites tested. Interestingly, butyrate was also the most potent HDAC inhibitor in a whole-cell HeLa Mad 38-based reporter gene assay, while all polyphenol metabolites and all other SCFAs tested were much less potent; some were completely inactive. The findings suggest that butyrate plays an outstanding role as endogenous HDAC inhibitor in the colon, and that other SCFAs and HDAC-inhibitory polyphenol metabolites present in the colon seem to play a much smaller role, probably because of their limited levels, their marked cytotoxicity and/or their limited intracellular availability.

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Crossref · 10.1016/j.jnutbio.2007.08.002

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Authors
Waldecker, M., Kautenburger, T., Daumann, H., Busch, C., & Schrenk, D.
Affiliations
University of Kaiserslautern (DE)
Corresponding author
Schrenk, Dieter
Venue
The Journal of Nutritional Biochemistry
Publisher
Elsevier BV
Published
2008-09
Volume
19
Issue
9
Pages
587-593
ISSN
0955-2863 (ISSN-L)
OpenAlex
W2016693701
Cited by
615
References
28
Citations by year
2026: 48 · 2025: 33 · 2024: 41 · 2023: 58 · 2022: 56 · 2021: 48 · 2020: 57 · 2019: 48 · 2018: 43 · 2017: 30 · 2016: 29 · 2015: 26 · 2014: 24 · 2013: 26 · 2012: 17
FWCI
4.25
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Nutritional Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
Bundesministerium für Bildung und Forschung
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
histone deacetylase inhibition, short-chain fatty acids, butyrate, polyphenol metabolites, caffeic acid, p-coumaric acid, colon cancer chemoprevention, colorectal cancer, HT-29 cells, propionate
MeSH terms
Antineoplastic Agents, Colon, Fatty Acids, Volatile, Flavonoids, HeLa Cells, Humans, Phenols, Phenylacetates, Phenylpropionates, HT29 Cells, Histone Deacetylase Inhibitors, Polyphenols

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