Glucuronidation in the Caco-2 human intestinal cell line: induction of UDP-glucuronosyltransferase 1*6.
The ability of the differentiated human intestinal cell line, Caco-2, to glucuronidate various endobiotic and xenobiotic molecules was investigated. Glucuronidation of hydroxylated or carboxylic acid compounds such as 1-naphthol, thymol, androsterone, estriol, hyodeoxycholic acid, lithocholic acid, chloramphenicol, paracetamol and morphine could be determined in microsomal fractions of Caco-2 cells. The activity toward 1-naphthol was the highest glucuronidation activity measured in Caco-2 cells. This activity was specifically increased four-fold upon addition of beta-naphthoflavone into culture medium but not by rifampicine or clofibrate and was related to a biosynthesis of UDP-glucuronosyltransferase 1*6 (UGT1*6). alpha-Naphthoflavone did not affect the inducing property of beta-naphthoflavone. 7-Ethoxyresorufin-O-dealkylation activity, supported by cytochrome P4501A1, was induced more than 1000-times in Caco-2 cells by beta-naphthoflavone treatment, and this effect was partially abolished by alpha-naphthoflavone treatment. The results suggest that several isoforms, including UGT1*6, are expressed in Caco-2 cells.
Abid
A
A
Centre du Médicament, URA CNRS 597, Faculté des Sciences Pharmaceutiques et Biologiques, Nancy, France.
Bouchon
I
I
Siest
G
G
Sabolovic
N
N
D001571:Benzoflavones / Q000494:pharmacology; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000096:biosynthesis* / Q000378:metabolism; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007422:Intestines / Q000201:enzymology; D007527:Isoenzymes / Q000096:biosynthesis* / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology; D009284:Naphthols / Q000378:metabolism; D010088:Oxidoreductases / Q000096:biosynthesis; D015262:Xenobiotics / Q000378:metabolism; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D006728:Hormones; D007527:Isoenzymes; D009284:Naphthols; D015262:Xenobiotics; C029350:1-naphthol; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D014453:Glucuronosyltransferase