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Suppression of CYP1A1 Expression by Naringenin in Murine Hepa-1c1c7 Cells  

Kim, Ji-Young (Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University)
Han, Eun-Hee (Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University)
Shin, Dong-Weon (Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University)
Jeong, Tae-Cheon (College of Pharmacy, Yeungnam University)
Lee, Eung-Seok (College of Pharmacy, Yeungnam University)
Woo, Eun-Rhan (Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University)
Jeong, Hye-Gwang (Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University)
Publication Information
Archives of Pharmacal Research / v.27, no.8, 2004 , pp. 857-862 More about this Journal
Abstract
Naringenin, dietary flavonoid, is antioxidant constituents of many citrus fruits. In the present study, we investigated the effect of naringenin on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible CYP1 A 1 gene expression in mouse hepatoma Hepa-1c1c7 cells. Naringenin alone did not affect CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity. In contrast, the TCDD-inducible EROD activities were markedly reduced upon concomitant treatment with TCDD and naringenin in a dose dependent manner. TCDD-induced CYP1A1 mRNA level was also markedly suppressed by naringenin. A transient transfection assay using dioxin-response element (DRE)-linked luciferase and electrophoretic mobility shift assay revealed that naringe-nin reduced transformation of the aryl hydrocarbons receptor(AhR) to a form capable of specif-ically binding to the DRE sequence in the promoter of the CYP1A1 gene. These results suggest the down regulation of the CYP1A1 gene expression by either naringenin in Hepa-1c1c7 cells might be antagonism of the DRE binding potential of nuclear AhR.
Keywords
Naringenin; CYP1A1; Ah receptor; Dioxin-response element;
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