Dietary Fiber Enhances a Tumor Suppressor Signaling Pathway in the Gut

    loading  Checking for direct PDF access through Ovid

Abstract

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)-β 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-β 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-β 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-β-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-β 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-β-induced Smad3 phosphorylation and potentiated TGF-β-induced PAI-1 expression. NaB and TGF-β synergistically inhibited anchorage-independent growth of Akt-transformed RIE-1 cells.

Conclusions:

These results demonstrate that NaB induces Smad3 and potentiates TGF-β 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.

Related Topics

    loading  Loading Related Articles