Butyrate and the colonocyte

Abstract

Butyrate is produced in the colon of mammals as a result of microbial fermentation of dietary fiber, undigested starch, and proteins. Butyrate may be an important protective agent in colonic carcinogenesis. Trophic effects on normal colonocytes in vitro and in vivo are induced by butyrate. In contrast, butyrate arrests the growth of neoplastic colonocytes and inhibits the preneoplastic hyperproliferation induced by some tumour promoters in vitro. We speculate that selective effects on G-protein activation may explain this paradox of butyrate's effects in normal versus neoplastic colonocytes. Butyrate induces differentiation of colon cancer cell lines. It also regulates the expression of molecules involved in colonocyte growth and adhesion and inhibits the expression of several protooncogenes relevant to colorectal carcinogenesis. Additional studies are needed to evaluate butyrate's antineoplastic effects in vivo and to understand its mechanism(s) of action.

Butyrate Induces Necrotic Cell Death in Murine Colonic Epithelial Cell MCE301

“…[18][19][20][21] The pro-apoptotic effects of butyrate are mediated via up-regulation of pro-apoptotic proteins, such as Bax and Bak, down-regulation of Bcl-Xl and the activation of caspases such as caspase-3. 22) One of the major apoptosis pathways is triggered by the release of mitochondrial apoptogenic protein, cytochrome c. Cytosolic cytochrome c binds to the CED-4 homolog Apaf-1 and induces caspase-9-dependent activation of caspase-3.…”

Butyrate induced Caco-2 cell apoptosis is mediated via the mitochondrial pathway

“…[2][3][4][5][6] In the present study, we analysed the signalling sequence in Caco-2 cells undergoing apoptosis after stimulation with butyrate. We observed activation of the caspase cascade after an interval of 12-16 hours, in concert with previous reports.…”

“…It has long been established that SCFAs play a critical role in maintaining homeostatic cell turnover in the colonic epithelium. 6 Besides its role as a preferred energy source for normal colonic epithelial cells, butyrate was shown to possess potent anticancer effects on transformed colonocytes. Recent data suggest that the main mechanism responsible for this antitumoral effect of butyrate is induction of apoptosis.…”

Butyrate Suppression of Colonocyte NF-κB Activation and Cellular Proteasome Activity

“…Short chain fatty acids benefit the colonic mucosa in a number of ways (1)(2)(3)(4)(5). Colonocytes utilize short chain fatty acids as their primary energy source, and evidence has been obtained that they undergo apoptosis in its absence (2,(5)(6)(7).…”

“…Interestingly, short chain fatty acids, particularly butyrate, have the opposite effect on transformed cells in culture, inducing rather than suppressing apoptosis (2, 8 -10). The ability of butyrate to induce cancer cell apoptosis may contribute to the cancer preventive activities of dietary fiber (1,5,6,11,12). Short chain fatty acids can also suppress intestinal inflammation: butyrate is effective for treating selected inflammatory conditions of the distal alimentary tract (13)(14)(15).…”