Kim Ji Young, Han Eun Hee, Shin Dong Weon, Jeong Tae Cheon, Lee Eung Seok, Woo Eun-Rhan, Jeong Hye Gwang
Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, Kwangju 501-759, Korea.
Arch Pharm Res. 2004 Aug;27(8):857-62. doi: 10.1007/BF02980179.
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 CYP1A1 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 naringenin reduced transformation of the aryl hydrocarbons receptor(AhR) to a form capable of specifically 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.
柚皮素是一种膳食类黄酮，是多种柑橘类水果中的抗氧化成分。在本研究中，我们调查了柚皮素对小鼠肝癌Hepa-1c1c7细胞中2,3,7,8-四氯二苯并对二恶英（TCDD）诱导的CYP1A1基因表达的影响。单独使用柚皮素不会影响CYP1A1特异性7-乙氧基异吩恶唑酮O-脱乙基酶（EROD）活性。相反，在与TCDD和柚皮素同时处理时，TCDD诱导的EROD活性以剂量依赖性方式显著降低。柚皮素也显著抑制了TCDD诱导的CYP1A1 mRNA水平。使用二恶英反应元件（DRE）连接的荧光素酶进行的瞬时转染试验和电泳迁移率变动分析表明，柚皮素减少了芳烃受体（AhR）向能够特异性结合CYP1A1基因启动子中DRE序列的形式的转化。这些结果表明，Hepa-1c1c7细胞中柚皮素可能通过拮抗核AhR的DRE结合潜力来下调CYP1A1基因表达。
