Potentiation of butyrate-induced differentiation in human colon tumor cells by deoxycholate.
Human colon adenocarcinoma cells, treated with deoxycholate for 24 h prior to exposure to 1 mM butyrate, exhibited dose-dependent increases in the activities of three markers of colonic differentiation (alkaline phosphatase, lactase and CEA). Treatment with deoxycholate alone, for 24 h or longer, did not increase the secretion of CEA or the activities of either of the brush border-associated enzyme activities. Increases in differentiation markers were found to be bile acid-specific. Pretreatment with either dehydrocholic acid or cholic acid, even at cytotoxic concentrations, led to no significant butyrate-induced increases in brush-border associated hydrolase activities. The addition of a bacterial superoxide dismutase decreased the short-term cytotoxicity of deoxycholate and increased the maturation-potentiating effects of the bile acid in HCT-116 DO cells. The results of these studies demonstrate that bile acids, which are commonly thought to have tumor promoting activities in vivo, may also have physiological effects which serve to limit carcinogenic processes in the human colon by potentiating tumor cell differentiation.
Section of Gastroenterology, Northwestern University Medical School, Chicago, IL 60611.
T K
TK
Desai
D F
DF
Nathan
M J
MJ
Morin
D000230:Adenocarcinoma / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D000469:Alkaline Phosphatase / Q000096:biosynthesis*; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002454:Cell Differentiation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D043322:Lactase; D013482:Superoxide Dismutase / Q000494:pharmacology; D001616:beta-Galactosidase / Q000096:biosynthesis*
D002087:Butyrates; D003840:Deoxycholic Acid; D020148:Butyric Acid; D013482:Superoxide Dismutase; D000469:Alkaline Phosphatase; D043322:Lactase; D001616:beta-Galactosidase