title: Butyrate modulates antioxidant enzyme expression in malignant and non-malignant human colon tissues.
abstract: The induction of antioxidant enzymes is an important mechanism in colon cancer chemoprevention, but the response of human colon tissue to butyrate, a gut fermentation product derived from dietary fiber, remains largely unknown. Therefore, our study investigated the effect of a butyrate treatment on catalase (CAT) and superoxide dismutase (SOD2) in matched human colon tissues of different transformation stages (n = 3-15 in each group) ex vivo. By performing quantitative real-time PCR, Western blot, and spectrophotometric measurements, we found an increase in SOD2 at expression and activity level in colonic adenocarcinomas (mRNA: 1.96-fold; protein: 1.41-fold, activity: 1.8-fold; P < 0.05). No difference was detectable for CAT between normal, adenoma, and carcinoma colon tissues. Treatment of normal colon epithelium (12 h) with a physiologically relevant concentration of butyrate (10 mM) resulted in a significant increase (P < 0.05) in CAT mRNA (1.24-fold) and protein (1.39-fold), without affecting the enzymatic activity. Consequently, preliminary experiments failed to show any protective effect of butyrate against H2 O2 -mediated DNA damage. Despite a significantly lowered SOD2 transcript (0.51-fold, P < 0.01) and, to a lesser extent, protein level (0.86-fold) after butyrate exposure of normal colon cells, the catalytic activity was significantly enhanced (1.19-fold, P < 0.05), suggesting an increased protection against tissue superoxide radicals. In malignant tissues, greater variations in response to butyrate were observed. Furthermore, both enzymes showed an age-dependent decrease in activity in normal colon epithelium (CAT: r = -0.49, P = 0.09; SOD2: r = -0.58, P = 0.049). In conclusion, butyrate exhibited potential antioxidant features ex vivo but cellular consequences need to be investigated more in depth.
authors.affiliation: Department of Nutritional Toxicology, Institute of Nutrition, Friedrich Schiller University Jena, Jena, Germany; Department of Single Cell and Single Molecule Techniques, Leibniz Institute for Age Research - Fritz Lipmann Institute, Jena, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Jahns
authors.forename: Anne
authors.initials: A
authors.lastname: Wilhelm
authors.forename: Nadja
authors.initials: N
authors.lastname: Jablonowski
authors.forename: Henning
authors.initials: H
authors.lastname: Mothes
authors.forename: Karl Otto
authors.initials: KO
authors.lastname: Greulich
authors.forename: Michael
authors.initials: M
authors.lastname: Glei
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000378:metabolism; D002087:Butyrates / Q000494:pharmacology*; D002374:Catalase / Q000235:genetics* / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D000975:Antioxidants; D002087:Butyrates; D002374:Catalase; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2
keywords: catalase; chemoprevention; colorectal cancer; dietary fiber; short chain fatty acids; superoxide dismutase 2