Differential regulation of activator protein 1 activity by glycyrrhizin.
Glycyrrhizin, a major component of Glycyrrhiza uralensis (licorice) root, is a saponin and exhibits a number of pharmacological effects, including anti-inflammation, anti-ulcer, anti-allergy, and anticarcinogenesis. Activator protein I (AP-1), a nuclear transcription factor, consists of Jun/Fos heterodimers or Jun/Jun homodimers, and blocking of tumor promoter-induced AP-1 activity could inhibit induced cellular transformation. In order to elucidate the molecular mechanism of glycyrrhizin-induced anticarcinogenesis, effect of glycyrrhizin on the AP-1 activity in untreated and tumor promoter-12-O-tetradecanoylphorbol-13-acetate (TPA)-treated conditions was analyzed in this study. Glycyrrhizin induced the AP-1/TATA reporter activity in a dose-dependent fashion, which was judged by chloramphenicol acetyltransferase assay and electrophoretic mobility-shift assay. Similar results were observed in HepG2 and Vero cells, suggested that glycyrrhizin effect was cell type-independent. In addition, the cis element responsible for glycyrrhizin activity was AP-1 responsive element. Further analysis indicated that glycyrrhizin exhibited a different regulation on the AP-1 activity in untreated and TPA-treated cells. Glycyrrhizin induced the AP-1 activity in untreated cells, while it inhibited the TPA-induced AP-1 activation in TPA-treated cells. These results provide insight into the biological actions of glycyrrhizin and the molecular basis for the development of new chemoprotective agents for cancer.
Hsiang
Chien-Yun
CY
Department of Microbiology, China Medical College, Taichun, Taiwan.
Lai
I-Lu
IL
Chao
De-Cheng
DC
Ho
Tin-Yun
TY
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms; D011401:Promoter Regions, Genetic; D020218:Response Elements; D016385:TATA Box; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014709:Vero Cells
D016588:Anticarcinogenic Agents; D018808:Transcription Factor AP-1; D019695:Glycyrrhizic Acid; D013755:Tetradecanoylphorbol Acetate