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 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.
Bordonaro
Michael
M
Department of Pharmacology and Developmental Therapeutics Program, Cancer Center, Yale University School of Medicine, New Haven, Connecticut, USA. michael.bordonaro@yale.edu
Lazarova
Darina L
DL
Sartorelli
Alan C
AC
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002087:Butyrates / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000178:diet therapy* / Q000378:metabolism* / Q000503:physiopathology; D004043:Dietary Fiber / Q000494:pharmacology* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D006801:Humans; D040242:Risk Reduction Behavior; D015398:Signal Transduction; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism*
D002087:Butyrates; D004043:Dietary Fiber; D051153:Wnt Proteins