title: Induction of cytochrome P450 1A1 expression by ginsenoside Rg1 and Rb1 in HepG2 cells.
abstract: Transcriptional activation of the human CYP1A1 gene (coding for cytochrome P450 1A1) is mediated by the aryl hydrocarbon receptor. In the present study we have examined interaction of the ginsenoside Rg1 and Rb1 with the carcinogen activation pathway mediated by the aryl hydrocarbon receptor in HepG2 cells. RT-PCR was used to determine the CYP1A1 mRNA levels. The results showed that in HepG2 cells CYP1A1 mRNA expression was significantly increased in a concentration- and time- dependent manner by ginsenoside Rg1 and Rb1. Ginsenoside Rg1 and Rb1 activated the DNA-binding capacity of the aryl hydrocarbon receptor for the xenobiotic responsive element of CYP1A1 as measured by the electrophoretic-mobility shift assay (EMSA). Rg1 and Rb1 were able to activate the ability of the aryl hydrocarbon receptor to bind to an oligonucleotide containing the xenobiotic-responsive element (XRE) of the cyp1a1 promoter. These results indicate that Rg1 and Rb1's effects on CYP1A1 induction are mediated by the aryl hydrocarbon receptor. Since CYP1A1 and aryl hydrocarbon receptor play important roles in carcinogenesis, development, differentiation and many other essential physiological functions, these results suggest that the chemopreventive effect of Panax ginseng may be due, in part, to ginsenoside Rg1 and Rb1's ability to compete with aryl hydrocarbons for both the aryl hydrocarbon receptor and CYP1A1. Rg1 and Rb1 may thus be natural ligands and substrates of the aryl hydrocarbon receptor or have relationship with aryl hydrocarbon receptor pathway. These properties might be of help for future studies in P. ginseng and chemoprevention in chemical-induced cancer.
authors.affiliation: Department of pharmacology and toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Wang
authors.forename: Xuan
authors.initials: X
authors.lastname: Ye
authors.forename: Zengchun
authors.initials: Z
authors.lastname: Ma
authors.forename: Qiande
authors.initials: Q
authors.lastname: Liang
authors.forename: Beibei
authors.initials: B
authors.lastname: Lu
authors.forename: Hongling
authors.initials: H
authors.lastname: Tan
authors.forename: Chengrong
authors.initials: C
authors.lastname: Xiao
authors.forename: Boli
authors.initials: B
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Gao
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D036145:Ginsenosides / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D005894:Panax / Q000737:chemistry; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D036145:Ginsenosides; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; C442759:ginsenoside Rb1; D019363:Cytochrome P-450 CYP1A1; C035054:ginsenoside Rg1