INDUCTION OF GLUTATHIONE-S-TRANSFERASE-PI BY SHORT-CHAIN FATTY-ACIDS IN THE INTESTINAL-CELL LINE CACO-2

Glutathione S-transferases (GSTs) are a multigene family of detoxifica tion and metabolizing enzymes that have been linked with the susceptib ility of tissues to environmental carcinogens. In addition to their ro le as the main energy source in the colonic mucosa, short-chain fatty acids (SCFAs) have been found to act as potent antiproliferative and d ifferentiating agents in various cancer cell lines. The objective of t his study was to evaluate the effects of SCFAs on the induction of GST pi in the intestine as a possible new anticarcinogenic mechanism of SC FAs. Studies were performed in Caco-2 cells, a cell line resembling fu nctionally normal enterocytes. Cells, cultured in DMEM supplemented wi th 10% fetal calf serum, were studied from day 0 dpc (days post conflu ence) until 21 dpc and culture. SCFAs (acetate, propionate, butyrate) were added to give a final concentration of 5 mmol L(-1). At 0, 3, 6, 9, 15, and 21 dpc, protein, lactate dehydrogenase (LDH), alkaline phos phatase (AP) and GSTpi were measured. Butyrate supplementation signifi cantly (P less than or equal to 0.01) increased GSTpi levels compared with controls in a concentration-dependent manner. The effect was dete ctable within 3 dpc with a maximum at 15 dpc. In contrast to butyrate, the other SCFAs tested had no (acetate) or little effect (propionate) . In conclusion, the data suggest that the anticancer effect of butyra te in part may be based on the induction of GSTpi activity, resulting in an enhanced detoxification capacity of the gut.