Butyrate and Wnt signaling: a possible solution to the puzzle of dietary fiber and colon cancer risk?

Studies on the protective role of dietary fiber and its breakdown product butyrate against colorectal cancer (CRC) have yielded inconsistent findings. We have reported that butyrate treatment of CRC cells in vitro modulates canonical Wnt signaling, a pathway which is constitutively activated in the...

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Bibliographic Details
Published in:Cell cycle (Georgetown, Tex.) Tex.), 2008-05, Vol.7 (9), p.1178-1183
Main Authors: Bordonaro, Michael, Lazarova, Darina L., Sartorelli, Alan C.
Format: Article
Language:English
Subjects:
Animals
Apoptosis - physiology
Binding
Biology
Bioscience
Butyrates - metabolism
Butyrates - pharmacology
Butyrates - therapeutic use
Calcium
Cancer
Cell
Cell Transformation, Neoplastic - drug effects
Cell Transformation, Neoplastic - metabolism
Colonic Neoplasms - diet therapy
Colonic Neoplasms - metabolism
Colonic Neoplasms - physiopathology
Cycle
Dietary Fiber - pharmacology
Dietary Fiber - therapeutic use
Drug Administration Schedule
Humans
Landes
Organogenesis
Proteins
Risk Reduction Behavior
Signal Transduction
Time Factors
Transcriptional Activation - drug effects
Transcriptional Activation - physiology
Wnt Proteins - metabolism
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Summary:Studies on the protective role of dietary fiber and its breakdown product butyrate against colorectal cancer (CRC) have yielded inconsistent findings. We have reported that butyrate treatment of CRC cells in vitro modulates canonical Wnt signaling, a pathway which is constitutively activated in the majority of CRCs. Analyses of ten human CRC cell lines exposed to butyrate have established that the levels of apoptosis in these cells are dependent upon the fold induction of canonical Wnt transcriptional activity. It is likely that the observed variability in the levels of induced Wnt activity and apoptosis in CRC cells in vitro reflects the existence of different CRC subtypes in vivo. The existence of CRC subtypes, individual- and population-specific variation in butyrate producing colonic microflora, and the time at which the colorectal lesions (early vs. late stage) are exposed to fiber/butyrate are all factors that may influence the protective role of fiber against CRC. We discuss the evidence by which these factors influence the effects of fiber on colonic tumorigenesis and outline experimental approaches for testing these hypotheses.
ISSN:1538-4101
1551-4005
DOI:10.4161/cc.7.9.5818