Inhibitory Effects of Ginsenoside-Rb1 on Activation of the 12-<i>O-</i>Tetradecanoylphorbol 13-Acetate-Induced Cyclooxygenase-2 Promoter

Abstract

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.