Signal transduction-mediated CYP1A1 induction by omeprazole in human HepG2 cells.

Article Details

Citation

Copy to clipboard

Kikuchi H, Hossain A

Signal transduction-mediated CYP1A1 induction by omeprazole in human HepG2 cells.

Exp Toxicol Pathol. 1999 Jul;51(4-5):342-6. doi: 10.1016/S0940-2993(99)80018-9.

PubMed ID

10445394 [ View in PubMed

]

Abstract

Benzimidazole compounds, such as omeprazole and thiabendazole, are a different type of CYP1A1-inducer from Ah receptor-ligands, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3-methylcholanthrene. In HepG2 cells, the commonly used tyrosine kinase-inhibitors, herbimycin-A and a series of tyrphostins, inhibited the induction of CYP1A1 produced by treatment with TCDD. Genistein, another type of tyrosine kinase inhibitor, inhibited the induction of CYP 1A1 whether it was produced by omeprazole or TCDD; however, this inhibition was caused by a dual effect of genistein, that is an anti-tyrosine kinase and an anti-topoisomerase I effect. An antagonist of Ah receptor, 3'-methoxy-4'-aminoflavone (1 microM), did not inhibit the induction of CYP1A1 produced in HepG2 cells by omeprazole or alpha-naphthoflavone (50 microM), but this antagonist did inhibit that produced by TCDD. Thus, omeprazole appears to induce CYP1A1 by initiating a protein tyrosine kinase-mediated signal transduction pathway, a different pathway from that initiated by TCDD.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Omeprazole	Cytochrome P450 1A1	Protein	Humans	Unknown	Substrate Inducer	Details