Dietary fiber enhances a tumor suppressor signaling pathway in the gut

Khoa A. Nguyen, Yanna Cao, Justin R. Chen, Courtney Townsend, Tien C. Ko

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)619-625
Number of pages7
JournalAnnals of Surgery
Volume243
Issue number5
DOIs
StatePublished - May 2006

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Dietary Fiber
Transforming Growth Factors
Neoplasms
Colonic Neoplasms
Plasminogen Activator Inhibitor 1
Phosphorylation
Cell Line
Butyric Acid
Volatile Fatty Acids
Cyclooxygenase 2
Growth
Fermentation
Epithelial Cells
Gene Expression

ASJC Scopus subject areas

  • Surgery

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Dietary fiber enhances a tumor suppressor signaling pathway in the gut. / Nguyen, Khoa A.; Cao, Yanna; Chen, Justin R.; Townsend, Courtney; Ko, Tien C.

In: Annals of Surgery, Vol. 243, No. 5, 05.2006, p. 619-625.

Research output: Contribution to journalArticle

Nguyen, Khoa A. ; Cao, Yanna ; Chen, Justin R. ; Townsend, Courtney ; Ko, Tien C. / Dietary fiber enhances a tumor suppressor signaling pathway in the gut. In: Annals of Surgery. 2006 ; Vol. 243, No. 5. pp. 619-625.
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