The gut fermentation product butyrate, a chemopreventive agent, suppresses glutathione S-transferase theta (hGSTT1) and cell growth more in human colon adenoma (LT97) than tumor (HT29) cells.
OBJECTIVE
The gut fermentation product of dietary fiber, butyrate, inhibits growth of HT29, an established tumor cell line. It also induces detoxifying enzymes belonging to the glutathione S-transferase family (GSTs), namely hGSTM2, hGSTP1, hGSTA4, but not of hGSTT1 . Here we investigated kinetics of effects in HT29 and compared sensitivities with preneoplastic LT97 colon adenoma cells, to assess mechanisms of colon cancer chemoprevention in two stages of cell transformation.


METHODS
We determined cell growth after butyrate treatment by quantifying DNA, GST expression by Northern/Western Blotting or biochemical analysis and butyrate consumption by measuring the residual concentrations in the cell culture supernatants. Stability of GST-theta (hGSTT1) mRNA was assessed in HT29 cells after inhibition of transcription with actinomycin D.


RESULTS
LT97 adenoma cells consumed twofold more butyrate and were more sensitive to growth inhibition than HT29 (EC(50)1.9 mM and 4.0 mM, respectively). Butyrate did not induce GSTs, but instead reduced hGSTT1 in LT97 and HT29.


CONCLUSIONS
Butyrate has suppressing-agent activities in human colon cells by inhibiting two survival factors, namely hGSTT1 and cell growth, with LT97 more sensitive than HT29. These findings indicate that butyrate formation in the gut lumen of humans could be protective by reducing survival of transformed colon cells.
Kautenburger
Tanja
T
Department of Nutritional Toxicology, Institute for Nutrition, Friedrich-Schiller-University, Jena, Germany.
Beyer-Sehlmeyer
Gabriele
G
Festag
Grit
G
Haag
Natja
N
Kühler
Stephanie
S
Küchler
Alma
A
Weise
Anja
A
Marian
Brigitte
B
Peters
Wilbert H M
WH
Liehr
Thomas
T
Claussen
Uwe
U
Pool-Zobel
Beatrice L
BL
D000236:Adenoma / Q000517:prevention & control*; D015152:Blotting, Northern; D015153:Blotting, Western; D002087:Butyrates / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D004043:Dietary Fiber / Q000378:metabolism; D005982:Glutathione Transferase / Q000187:drug effects*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D012333:RNA, Messenger / Q000032:analysis
D002087:Butyrates; D004043:Dietary Fiber; D012333:RNA, Messenger; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase