Previous studies from our laboratory on
tumor cells suggest that
phytosterols stimulate
ceramide production, which was associated with cell growth inhibition and stimulation of apoptosis. The objective of the present study was to examine the effect of
phytosterols on
ceramide metabolism in small intestinal cells that represent the first cells in contact with dietary
phytosterols. Caco(2) cells, an accepted model for human intestinal epithelial cells, were used in this study.
Ceramide and
ceramide-containing
lipids were examined by labeling the
ceramide pool with (3)H-serine. Cells were supplemented with 16 microM of
sterols (
cholesterol,
beta-sitosterol or
campesterol) for 16 days postconfluence and continued to differentiate. Of the two
phytosterols,
beta-sitosterol, but not
campesterol, induced more than double the
serine labeling when compared with
cholesterol. This increase was uniform in
sphingomyelin (SM),
ceramide and
sphingosine labeling.
Sterols had no effect on SM concentration in the cells. In addition,
sterol had no effect on the activity of SM synthase or sphingomyelinases. There was an inhibition of
ceramidases with
campesterol supplementation. These data suggest that the observed increases in SM and
sphingosine labeling were due to an increase in
ceramide turnover. The increase in
ceramide turnover with
beta-sitosterol supplementation was not associated with growth inhibition but was with increases in
ceramide glycosylation products such as
cerebrosides and
gangliosides. It was concluded that
beta-sitosterol has no effect on differential Caco(2), a model of normal small intestinal cells. The increase in the glycosylated
ceramide products may offer a means to protect the cells from the harmful effect of
ceramide by excreting them with
lipoproteins.