Suppressive effects of alpha-Hederin on 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated murine Cyp1a-1 expression in the mouse hepatoma Hepa-1c1c7 cells.
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.
Jeong
H G
HG
Department of Biological Science, Chosun University, Kwangju, South Korea. hgjeong@mail.chosun.ac.kr
Lee
S S
SS
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D051379:Mice; D009828:Oleanolic Acid / Q000031:analogs & derivatives*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology; D012503:Saponins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004365:Drugs, Chinese Herbal; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D012503:Saponins; C010177:beta-hederin; D009828:Oleanolic Acid; D019363:Cytochrome P-450 CYP1A1