The short chain fatty acid, butyrate, stimulates MUC2 mucin production in the human colon cancer cell line, LS174T.
The short fatty acid, butyrate, which is produced by intestinal anaerobic bacteria in the colon, has inhibitory activity on histone deacetylases (HDACs). Treatment of the human colon cancer cell line, LS174T, with 1-2 mM sodium butyrate stimulated MUC2 mucin production, as determined by histological PAS staining of carbohydrate chains of mucin, and confirmed at the protein and mRNA levels by immunoblotting with anti-MUC2 antibody and real-time RT-PCR, respectively. Increases in acetylated histone H3 in the LS174T cells treated with butyrate suggest inhibition of HDACs in these cells. Butyrate-stimulated MUC2 production in the LS174T cells was inhibited by the MEK inhibitor, U0126, implicating the involvement of extracellular signal-regulated kinase (ERK) cascades in this process. Proliferation of the LS174T cells was inhibited by butyrate treatment. Although apoptotic nuclear DNA fragmentation could not be detected, cell-cycle arrest at the G0/G1 phase in the butyrate-treated cells was demonstrated by flow cytometry. Thus butyrate, an HDAC inhibitor, inhibits proliferation of LS174T cells but stimulates MUC2 production in individual cells.
Hatayama
Hajime
H
Molecular Biology Laboratory, Faculty of Bioresource Sciences, Akita Prefectural University, Akita 010-0195, Japan.
Iwashita
Jun
J
Kuwajima
Akiko
A
Abe
Tatsuya
T
D000230:Adenocarcinoma / Q000378:metabolism*; D002070:Butadienes / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism*; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D055262:Mucin-2; D009077:Mucins / Q000096:biosynthesis*; D009570:Nitriles / Q000494:pharmacology
D002070:Butadienes; D002087:Butyrates; C524625:MUC2 protein, human; D055262:Mucin-2; D009077:Mucins; D009570:Nitriles; C113580:U 0126; D020929:Mitogen-Activated Protein Kinase Kinases