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
B. Singh et al., 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, Carcinogenesis, 18(6), 1997, pp. 1265-1270
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.