Jeong H G, Lee S S
Department of Biological Science, Chosun University, Kwangju, South Korea.
Cancer Lett. 1999 Apr 26;138(1-2):131-7. doi: 10.1016/s0304-3835(98)00386-3.
Cultured mouse hepatoma cell line Hepa-1c1c7 cells were treated with alpha-Hederin to assess the role of alpha-Hederin in the process of Cyp1a-1 induction. Treatment of Hepa-1c1c7 cultures with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced Cyp1a-1, as indicated by analysis of 7-ethoxyresorufin O-deethylation (EROD) activity and Cyp1a-1 protein. When alpha-Hederin and TCDD were both added to cultures, TCDD-inducible EROD activity was greatly suppressed by alpha-Hederin in a dose-dependent manner. TCDD-induced Cyp1a-1 protein and mRNA levels were markedly reduced in the concomitant treatment of TCDD and alpha-Hederin consistent with EROD activity. Electrophoretic mobility shift assay using nuclear extraction of cells revealed that alpha-Hederin reduced transformation of the Ah receptor to a form capable of specifically binding to an oligonucleotide containing a dioxin-response element (DRE) sequence of the Cyp1a-1 gene. These results suggest that the suppressive effect of alpha-Hederin on TCDD-induced Cyp1a-1 gene expression in Hepa-1c1c7 cells might be an antagonist of the DNA binding potential of a nuclear Ah receptor.
用α-常春藤皂苷处理培养的小鼠肝癌细胞系Hepa-1c1c7细胞，以评估α-常春藤皂苷在Cyp1a-1诱导过程中的作用。用2,3,7,8-四氯二苯并对二恶英（TCDD）处理Hepa-1c1c7培养物可诱导Cyp1a-1，这通过7-乙氧基异吩恶唑酮O-脱乙基酶（EROD）活性分析和Cyp1a-1蛋白得以证实。当将α-常春藤皂苷和TCDD都添加到培养物中时，TCDD诱导的EROD活性被α-常春藤皂苷以剂量依赖的方式大大抑制。在TCDD和α-常春藤皂苷联合处理中，TCDD诱导的Cyp1a-1蛋白和mRNA水平与EROD活性一致，均显著降低。使用细胞的核提取物进行的电泳迁移率变动分析表明，α-常春藤皂苷减少了Ah受体向能够特异性结合含有Cyp1a-1基因二恶英反应元件（DRE）序列的寡核苷酸的形式的转化。这些结果表明，α-常春藤皂苷对Hepa-1c1c7细胞中TCDD诱导的Cyp1a-1基因表达的抑制作用可能是核Ah受体DNA结合潜能的拮抗剂。
