Inhibitory effects of ginsenoside-Rb1 on activation of the 12-O-tetradecanoylphorbol 13-acetate-induced cyclooxygenase-2 promoter.
We studied the inhibitory effects of ginsenoside-Rb1 (1) on 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced transcriptional activation of the cyclooxygenase-2 (COX-2) promoter. The suppressive activity of ginsenoside-Rb1 was characterized using COX-2 promoter-driven luciferase reporter plasmids in a transient transfection system. Ginsenoside-Rb1 at 100 microM inhibited TPA-induced transcriptional activation of the COX-2 promoter. To identify the cis-acting elements responsible for this inhibition, the effects of site-specific mutations in the COX-2 promoter region were examined. Inhibition by ginsenoside-Rb1 was not affected by mutations in nuclear factor-kappaB- or cAMP-responsive elements. However, the effects were abolished when the nuclear factor-interleukin-6 binding site was mutated, indicating that ginsenoside-Rb1 exerts its effects via this element. In conclusion, ginsenoside-Rb1 inhibits TPA-induced COX-2 promoter activity through the nuclear factor interleukin-6 binding site and not through the nuclear factor-kappaB or cAMP-responsive elements.
College of Life Science, Institute of Biotechnology, Department of Bioscience and Biotechnology, Sejong University, Seoul, Korea.
Wankyu
W
Park
Wonchung
W
Lim
Jungyoon
J
Cho
Hiroyasu
H
Inoue
Mee-Ra
MR
Rhyu
YoungJoo
Y
Lee
D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D051546:Cyclooxygenase 2 / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D005894:Panax; D008517:Phytotherapy; D013755:Tetradecanoylphorbol Acetate
D022782:CCAAT-Enhancer-Binding Protein-beta; D052246:Cyclooxygenase 2 Inhibitors; D036145:Ginsenosides; C442759:ginsenoside Rb1; D051546:Cyclooxygenase 2; D013755:Tetradecanoylphorbol Acetate