BUTYRATE CAN ACT AS A STIMULATOR OF GROWTH OR INDUCER OF APOPTOSIS INHUMAN COLONIC EPITHELIAL-CELL LINES DEPENDING ON THE PRESENCE OF ALTERNATIVE ENERGY-SOURCES

In vivo, butyrate is a major energy source for the colonic epithelium and is thought to stimulate proliferation, In contrast, butyrate in vi tro has been shown to inhibit proliferation and induce differentiation and apoptosis in colonic epithelial cells, Most colon cell cultures a re grown in medium containing high concentrations of glucose, whereas in vivo the main energy source used by the colon cells is butyrate, Th e aim of this study was to determine whether the apparent contrasting roles of butyrate in vivo and in vitro could be as a consequence of di fferences in glucose availability. The sensitivity of two human colore ctal tumour cell lines, one adenoma (S/RG/C2) and one carcinoma (HT29) to butyrate-induced growth inhibition and apoptosis was investigated to determine whether these cellular effects were altered under glucose depleted culture conditions, Glucose depletion resulted in increased apoptosis in both cell lines in the absence of butyrate, Butyrate in s tandard culture conditions (containing 25 mM glucose and 1 mM pyruvate ) inhibited growth and induced apoptosis in both cell lines, However, low concentrations of butyrate in glucose depleted culture conditions (i,e, standard growth medium without glucose and pyruvate supplements) were found to reduce apoptosis induced by glucose deprivation and inc rease cell yield in both cell lines, The results show that in glucose depleted culture conditions, butyrate at low concentrations (0.5 mM fo r S/RG/CZ, and 0.5 and 2 mM for HT29 cells) was found to be growth sti mulatory whereas in the presence of glucose, these same concentrations of butyrate induced apoptosis, Thus, whether butyrate is growth stimu latory or growth inhibitory may depend on the availability of other en ergy sources, These observations may, in part, provide an explanation for the apparent opposite effects of butyrate on proliferation reporte d ira vivo and irt vitro.