Glucuronidation in the Caco-2 human intestinal cell line: induction of UDP-glucuronosyltransferase 1*6

Biochem Pharmacol. 1995 Aug 8;50(4):557-61. doi: 10.1016/0006-2952(95)00162-s.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Benzoflavones / pharmacology
  • Cell Line
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Enzyme Induction / drug effects
  • Glucuronosyltransferase / biosynthesis*
  • Glucuronosyltransferase / metabolism
  • Hormones / metabolism
  • Humans
  • Intestines / enzymology
  • Isoenzymes / biosynthesis*
  • Isoenzymes / metabolism
  • Microsomes, Liver / enzymology
  • Naphthols / metabolism
  • Oxidoreductases / biosynthesis
  • Xenobiotics / metabolism
  • beta-Naphthoflavone

Substances

  • Benzoflavones
  • Hormones
  • Isoenzymes
  • Naphthols
  • Xenobiotics
  • 1-naphthol
  • beta-Naphthoflavone
  • Cytochrome P-450 Enzyme System
  • Oxidoreductases
  • Cytochrome P-450 CYP1A1
  • Glucuronosyltransferase