Dietary fiber enhances a tumor suppressor signaling pathway in the gut

Ann Surg. 2006 May;243(5):619-25; discussion 625-7. doi: 10.1097/01.sla.0000216783.85214.c1.


Objective: To determine whether sodium butyrate (NaB), a major short-chain fatty acid produced in the human gut by bacterial fermentation of dietary fiber, enhances transforming growth factor (TGF)-beta signaling and potentiates its tumor suppressor activity in the gut.

Summary background data: The molecular mechanisms by which dietary fiber decreases the risk of colon cancers are poorly characterized. TGF-beta is an important tumor suppressor in the gut and has many similar biologic activities as NaB. Therefore, we hypothesized that the chemo-preventive effects of NaB are mediated in part by enhancing TGF-beta signaling and its tumor suppressor function in the gut.

Methods: The effects of NaB on Smad3 expression in rat intestinal epithelial (RIE-1) cells and 6 human colon cancer cell lines were examined. The effects of NaB on TGF-beta-induced Smad3 phosphorylation and plasminogen activator inhibitor-1 (PAI-1) and cyclooxygenase-2 (COX-2) gene expression were also examined in RIE-1 cells. Finally, the effects of NaB and TGF-beta on anchorage-independent growth were examined in Akt-transformed RIE-1 cells.

Results: NaB induced Smad3 in RIE-1 cells and in 4 human colon cancer cell lines. NaB enhanced TGF-beta-induced Smad3 phosphorylation and potentiated TGF-beta-induced PAI-1 expression. NaB and TGF-beta synergistically inhibited anchorage-independent growth of Akt-transformed RIE-1 cells.

Conclusions: These results demonstrate that NaB induces Smad3 and potentiates TGF-beta signaling and its tumor suppressor activity in gut epithelial cells. Our data reveal a novel molecular mechanism that may explain in part the beneficial effects of dietary fiber in decreasing the risk of colon cancers.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Butyric Acid / pharmacology*
  • Cells, Cultured
  • Colonic Neoplasms / prevention & control
  • Dietary Fiber* / therapeutic use
  • Epithelial Cells / metabolism*
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / physiology
  • Rats
  • Signal Transduction*
  • Smad3 Protein / biosynthesis*
  • Transforming Growth Factor beta / drug effects
  • Transforming Growth Factor beta / physiology*


  • Dietary Fiber
  • SMAD3 protein, human
  • Smad3 Protein
  • Transforming Growth Factor beta
  • Butyric Acid