Nonsteroidal anti-inflammatory drugs and phenols glucuronidation in Caco-2 cells: identification of the UDP-glucuronosyltransferases UGT1A6, 1A3 and 2B7

Life Sci. 2000;67(2):185-96. doi: 10.1016/s0024-3205(00)00616-0.


Glucuronidation of phenols (1-naphthol, 4-methylumbelliferone) and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ketoprofen, naproxen and carprofen was investigated in human colon carcinoma Caco-2 cell clones. Glucuronidation of these substances was highly effective in microsomes of the clones PD-7 and TC-7, but much lower in the PF-11 clone. The activity increased up to a maximum after 21 days of culture. RT-PCR experiments indicated that the PD-7 and TC-7 clones expressed the UDP-glucuronosyltransferase (UGT) isoforms UGT1A6, UGT1A3 and UGT2B7, which could account for the glucuronidation of phenols and carboxylic acids observed. Beta-naphthoflavone stimulated by 2-fold the enzyme activity toward 1-naphthol in PD-7 and TC-7 clones, but not in PF-11 cells. This increase was parallel to that of the UGT1A6 mRNA level. Glucuronidation of ketoprofen was also sensitive to the inducing effect of beta-naphthoflavone. Actinomycin D and cycloheximide did not affect the induction of UGT1A6 by beta-naphthoflavone, but suppressed that of ketoprofen UGT. The UGT1A3 mRNA content was enhanced by beta-naphthoflavone; by contrast, that of UGT2B7 was insensitive to the inducer. In conclusion, several UGT isoforms of both families 1 and 2, which glucuronidate phenols and carboxylic NSAIDs, have been identified in Caco-2 cells. They are differently sensitive to beta-naphthoflavone.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / metabolism*
  • Caco-2 Cells
  • Enzyme Induction / drug effects
  • Enzyme Inhibitors / pharmacology
  • Glucuronic Acid / metabolism
  • Glucuronosyltransferase / analysis
  • Glucuronosyltransferase / antagonists & inhibitors
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism*
  • Humans
  • Phenols / metabolism*
  • Protein Biosynthesis / drug effects
  • Transcription, Genetic / drug effects
  • Xenobiotics / metabolism
  • beta-Naphthoflavone / pharmacology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Enzyme Inhibitors
  • Phenols
  • Xenobiotics
  • beta-Naphthoflavone
  • Glucuronic Acid
  • UDP-glucuronosyltransferase, UGT1A3
  • UDP-glucuronosyltransferase, UGT1A6
  • UGT2B7 protein, human
  • Glucuronosyltransferase