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.
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 humancolon 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 humancolon 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.
Authors: Ulrike Peters; Rashmi Sinha; Nilanjan Chatterjee; Amy F Subar; Regina G Ziegler; Martin Kulldorff; Robert Bresalier; Joel L Weissfeld; Andrew Flood; Arthur Schatzkin; Richard B Hayes Journal: Lancet Date: 2003-05-03 Impact factor: 79.321
Authors: Sheila A Bingham; Nicholas E Day; Robert Luben; Pietro Ferrari; Nadia Slimani; Teresa Norat; Françoise Clavel-Chapelon; Emmanuelle Kesse; Alexandra Nieters; Heiner Boeing; Anne Tjønneland; Kim Overvad; Carmen Martinez; Miren Dorronsoro; Carlos A Gonzalez; Timothy J Key; Antonia Trichopoulou; Androniki Naska; Paolo Vineis; Rosario Tumino; Vittorio Krogh; H Bas Bueno-de-Mesquita; Petra H M Peeters; Göran Berglund; Göran Hallmans; Eiliv Lund; Guri Skeie; Rudolf Kaaks; Elio Riboli Journal: Lancet Date: 2003-05-03 Impact factor: 79.321
Authors: Andrew R Conery; Yanna Cao; E Aubrey Thompson; Courtney M Townsend; Tien C Ko; Kunxin Luo Journal: Nat Cell Biol Date: 2004-04 Impact factor: 28.824
Authors: Yanna Cao; Xuxia Gao; Weili Zhang; Guohua Zhang; Anthony K Nguyen; Xianghua Liu; Fernando Jimenez; Charles S Cox; Courtney M Townsend; Tien C Ko Journal: Am J Physiol Gastrointest Liver Physiol Date: 2011-03-31 Impact factor: 4.052
Authors: Katherine B Schuetze; Matthew S Stratton; Weston W Blakeslee; Michael F Wempe; Florence F Wagner; Edward B Holson; Yin-Ming Kuo; Andrew J Andrews; Tonya M Gilbert; Jacob M Hooker; Timothy A McKinsey Journal: J Pharmacol Exp Ther Date: 2017-02-07 Impact factor: 4.030
Authors: Xuxia Gao; Yanna Cao; Wenli Yang; Chaojun Duan; Judith F Aronson; Cristiana Rastellini; Celia Chao; Mark R Hellmich; Tien C Ko Journal: Am J Physiol Gastrointest Liver Physiol Date: 2013-02-21 Impact factor: 4.052
Authors: Y Cao; X Liu; W Zhang; X Deng; H Zhang; Y Liu; L Chen; E A Thompson; C M Townsend; T C Ko Journal: Oncogene Date: 2009-01-12 Impact factor: 9.867
Authors: Chen Zhao; Ivan Ivanov; Edward R Dougherty; Terryl J Hartman; Elaine Lanza; Gerd Bobe; Nancy H Colburn; Joanne R Lupton; Laurie A Davidson; Robert S Chapkin Journal: Cancer Prev Res (Phila) Date: 2009-05-26