Effects of short-chain fatty acids on growth and differentiation of the human colon-cancer cell line HT29.
Short-chain fatty acids (SCFAs), namely butyrate, acetate and propionate, originate from the bacterial fermentation of dietary fibers and are the predominant anions present in the large bowel. Our study was carried out to investigate the effects of SCFAs on growth of the human adenocarcinoma cell line, HT29. The results show that, under our culture conditions, both propionate and butyrate inhibit growth of HT29 cells, whereas acetate has no significant effect. The antiproliferative effect of propionate or butyrate is associated with an inhibition of FCS-induced activation of ornithine decarboxylase (ODC), a key enzyme of polyamine metabolism. Inhibition of growth induced by either propionate or butyrate is not reversed by the addition of putrescine, which reveals that these SCFAs are not acting solely on the ODC/polyamine system. Our data show that propionate and butyrate, unlike acetate, induce an increase in alkaline phosphatase activity, which reflects a more differentiated phenotype than that of untreated control cells. Taken together, our results suggest that propionate, like butyrate, may play an important role in the physiology of the colon and could partially account for the protective effect of dietary fibers with respect to colon carcinogenesis.
Gamet
L
L
INSERM, U 317, CHU Rangueil, Toulouse, France.
Daviaud
D
D
Denis-Pouxviel
C
C
Remesy
C
C
Murat
J C
JC
D000085:Acetates / Q000494:pharmacology*; D019342:Acetic Acid; D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology*; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology*; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D011422:Propionates / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000085:Acetates; D002087:Butyrates; D011422:Propionates; D020148:Butyric Acid; D009955:Ornithine Decarboxylase; C029658:propionic acid; D019342:Acetic Acid