INCREASE OF AHR ACTIVITY BY OMEPRAZOLE CAN BE REDUCED IN THE PRESENCE OF RESVERATROL OR QUERCETIN
The AHR is a transcription factor that is ligand-activated and controls many genes, including CYP1A1. Some known ligands that activate the AHR are B[a]P, omeprazole, resveratrol, and quercetin. B[a]P is a known carcinogen and a common environmental toxin. It has shown high activation of the AHR and is subsequently metabolically activated by CYP1A1 to a highly reactive diol epoxide that damages DNA. Omeprazole is a proton pump inhibitor that acts as a non-classical ligand for the AHR. However, resveratrol (a stilbenoid) and quercetin (a bioflavonoid), which are naturally found in certain fruits and vegetables, have shown minimal activation of the AHR. We used the HepG2 40/6 human liver cell line to analyze activation of the AHR by these compounds, using a luciferase reporter assay. Our results indicate that omeprazole treatment was able to increase AHR-mediated transcription in these cells by 150%. This could then be completely inhibited by the presence of 100 µM quercetin or 100 µM resveratrol, although not with 10 µM resveratrol. Since AHR activation is associated with an increased risk of cancer, these data suggests that omeprazole, which is commonly-prescribed and available over-the-counter, could further enhance carcinogenesis in patients taking this drug. Our data also indicate that including foods rich in bioflavonoids or resveratrol in one’s diet could be chemopreventative.
YHC Undergraduate Research Initiative
Galdamez*, Ana E. and Schroeder, Jennifer C.
"INCREASE OF AHR ACTIVITY BY OMEPRAZOLE CAN BE REDUCED IN THE PRESENCE OF RESVERATROL OR QUERCETIN,"
Georgia Journal of Science, Vol. 76, No. 1, Article 52.
Available at: https://digitalcommons.gaacademy.org/gjs/vol76/iss1/52