Dietary Fiber Enhances a Tumor Suppressor Signaling Pathway in the Gut
| Autor: | Khoa A. Nguyen, Yanna Cao, Justin R. Chen, Tien C. Ko, Courtney M. Townsend |
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| Rok vydání: | 2006 |
| Předmět: |
Dietary Fiber
medicine.medical_specialty Tumor suppressor gene law.invention chemistry.chemical_compound Transforming Growth Factor beta law Internal medicine Animals Humans Medicine Smad3 Protein Intestinal Mucosa Cells Cultured chemistry.chemical_classification business.industry Fatty acid Epithelial Cells Sodium butyrate Original Articles Rats Cell biology Endocrinology chemistry Colonic Neoplasms Butyric Acid Suppressor Surgery Fermentation Dietary fiber Signal transduction business Signal Transduction Transforming growth factor |
| Zdroj: | Annals of Surgery. 243:619-627 |
| ISSN: | 0003-4932 |
| DOI: | 10.1097/01.sla.0000216783.85214.c1 |
| Popis: | 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.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.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.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.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. |
| Databáze: | OpenAIRE |
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