p300 Knockout Promotes Butyrate Resistance.

Dietary fiber is linked to a reduced risk of colorectal cancer (CRC), and this protective activity is likely due to its fermentation product, butyrate. Dependent upon the hyperactivation of Wnt signaling, butyrate represses CRC cell growth and induces apoptosis. However, resistance to butyrate activity may allow for CRC development even in the context of relatively high fiber intake. We have previously determined that CRC cells resistant to butyrate are deficient in p300 expression. The histone acetylase p300 influences colonic cell signaling and physiology through effects on Wnt signaling. In this short research communication, we report that p300 knockout CRC cells exhibit butyrate resistance, and the re-introduction of p300 expression in p300 knockout CRC cells restores butyrate sensitivity. Microarray data on gene expression associated with butyrate sensitivity are presented and discussed.