Butyrate alters expression of cytochrome P450 1A1 and metabolism of benzo[a]pyrene via its histone deacetylase activity in colon epithelial cell models
Language English Country Germany Media print-electronic
Document type Journal Article
PubMed
27830268
DOI
10.1007/s00204-016-1887-4
PII: 10.1007/s00204-016-1887-4
Knihovny.cz E-resources
- Keywords
- Butyrate, CYP1A1, Colon epithelial cells, DNA adducts, Histone deacetylases, Polycyclic aromatic hydrocarbons,
- MeSH
- DNA Adducts drug effects metabolism MeSH
- Benzo(a)pyrene metabolism pharmacokinetics MeSH
- beta Catenin metabolism MeSH
- HT29 Cells MeSH
- Cytochrome P-450 CYP1A1 genetics metabolism MeSH
- HCT116 Cells MeSH
- Histone Deacetylase 1 antagonists & inhibitors metabolism MeSH
- Histones metabolism MeSH
- Histone Deacetylase Inhibitors pharmacology MeSH
- Colon drug effects metabolism MeSH
- Butyric Acid pharmacology MeSH
- Humans MeSH
- Inactivation, Metabolic MeSH
- Enhancer Elements, Genetic drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- DNA Adducts MeSH
- Benzo(a)pyrene MeSH
- beta Catenin MeSH
- CTNNB1 protein, human MeSH Browser
- CYP1A1 protein, human MeSH Browser
- Cytochrome P-450 CYP1A1 MeSH
- HDAC1 protein, human MeSH Browser
- Histone Deacetylase 1 MeSH
- Histones MeSH
- Histone Deacetylase Inhibitors MeSH
- Butyric Acid MeSH
Butyrate, a short-chain fatty acid produced by fermentation of dietary fiber, is an important regulator of colonic epithelium homeostasis. In this study, we investigated the impact of this histone deacetylase (HDAC) inhibitor on expression/activity of cytochrome P450 family 1 (CYP1) and on metabolism of carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP), in colon epithelial cells. Sodium butyrate (NaBt) strongly potentiated the BaP-induced expression of CYP1A1 in human colon carcinoma HCT116 cells. It also co-stimulated the 7-ethoxyresorufin-O-deethylase (EROD) activity induced by the 2,3,7,8-tetrachlorodibenzo-p-dioxin, a prototypical ligand of the aryl hydrocarbon receptor. Up-regulation of CYP1A1 expression/activity corresponded with an enhanced metabolism of BaP and formation of covalent DNA adducts. NaBt significantly potentiated CYP1A1 induction and/or metabolic activation of BaP also in other human colon cell models, colon adenoma AA/C1 cells, colon carcinoma HT-29 cells, or in NCM460D cell line derived from normal colon mucosa. Our results suggest that the effects of NaBt were due to its impact on histone acetylation, because additional HDAC inhibitors (trichostatin A and suberanilohydroxamic acid) likewise increased both the induction of EROD activity and formation of covalent DNA adducts. NaBt-induced acetylation of histone H3 (at Lys14) and histone H4 (at Lys16), two histone modifications modulated during activation of CYP1A1 transcription, and it reduced binding of HDAC1 to the enhancer region of CYP1A1 gene. This in vitro study suggests that butyrate, through modulation of histone acetylation, may potentiate induction of CYP1A1 expression, which might in turn alter the metabolism of BaP within colon epithelial cells.
Department of Chemistry and Toxicology Veterinary Research Institute 62100 Brno Czech Republic
Department of Experimental Biology Faculty of Science Masaryk University 61137 Brno Czech Republic
References provided by Crossref.org
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