Butyrate alters expression of cytochrome P450 1A1 and metabolism of benzo[a]pyrene via its histone deacetylase activity in colon epithelial cell models.
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 Cytokinetics, Institute of Biophysics, The Czech Academy of Sciences, Královopolská 135, 61265, Brno, Czech Republic.|Department of Experimental Biology, Faculty of Science, Masaryk University, 61137, Brno, Czech Republic.
Ondřej
O
Zapletal
Department of Cytokinetics, Institute of Biophysics, The Czech Academy of Sciences, Královopolská 135, 61265, Brno, Czech Republic.|Department of Experimental Biology, Faculty of Science, Masaryk University, 61137, Brno, Czech Republic.
Zuzana
Z
Tylichová
Department of Chemistry and Toxicology, Veterinary Research Institute, 62100, Brno, Czech Republic.
Jiří
J
Neča
Department of Chemistry and Toxicology, Veterinary Research Institute, 62100, Brno, Czech Republic.
Jiří
J
Kohoutek
Department of Chemistry and Toxicology, Veterinary Research Institute, 62100, Brno, Czech Republic.
Miroslav
M
Machala
Department of Genetic Ecotoxicology, Institute of Experimental Medicine, The Czech Academy of Sciences, 14220, Prague, Czech Republic.
Alena
A
Milcová
Department of Genetic Ecotoxicology, Institute of Experimental Medicine, The Czech Academy of Sciences, 14220, Prague, Czech Republic.
Michaela
M
Pokorná
Department of Genetic Ecotoxicology, Institute of Experimental Medicine, The Czech Academy of Sciences, 14220, Prague, Czech Republic.
Jan
J
Topinka
INCELL Corporation LLC, San Antonio, TX, 78249, USA.
Mary Pat
MP
Moyer
Department of Cytokinetics, Institute of Biophysics, The Czech Academy of Sciences, Královopolská 135, 61265, Brno, Czech Republic.
Jiřina
J
Hofmanová
Department of Cytokinetics, Institute of Biophysics, The Czech Academy of Sciences, Královopolská 135, 61265, Brno, Czech Republic.
Alois
A
Kozubík
Department of Cytokinetics, Institute of Biophysics, The Czech Academy of Sciences, Královopolská 135, 61265, Brno, Czech Republic. vondracek@ibp.cz.
Jan
http://orcid.org/0000-0003-4071-1969
J
Vondráček
D001564:Benzo(a)pyrene / Q000378:metabolism / Q000493:pharmacokinetics*; D020148:Butyric Acid / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D018736:DNA Adducts / Q000187:drug effects / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000187:drug effects; D045325:HCT116 Cells; D019073:HT29 Cells; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D051176:beta Catenin / Q000378:metabolism
C495270:CTNNB1 protein, human; D018736:DNA Adducts; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D051176:beta Catenin; D020148:Butyric Acid; D001564:Benzo(a)pyrene; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1
Butyrate; CYP1A1; Colon epithelial cells; DNA adducts; Histone deacetylases; Polycyclic aromatic hydrocarbons