Inhibitory effect of emodin on tumor invasion through suppression of activator protein-1 and nuclear factor-κB

Abstract

3-Methyl-1,6,8-trihydroxyanthraquinone (emodin) is an active component from the rhizome of Rheum palmatum, a widely used traditional Chinese herb. In this study, we found that emodin significantly inhibited 12-O-tetradecanoylphorbol- 13-acetate (TPA)-induced in vitro invasion of human cancer cells including HSC5 and MDA-MB-231 cells. Matrix metalloproteinases (MMPs) are known to be associated with cancer invasion. Zymographic analysis showed that emodin suppressed TPA-induced MMP-9 activity in a concentration-dependent manner. We further demonstrated that emodin reduced the transcriptional activity of activator protein-1 (AP-1) and nuclear factor kappaB (NF-κB), two important nuclear transcription factors involved in MMP-9 expression. Emodin suppressed the phosphorylation of two mitogen-activated protein kinases, extracellular signal-regulated protein kinase and c-Jun N-terminal kinase, but not p38 kinase, leading to reduced c-Jun phosphorylation and AP-1 DNA-binding. Moreover, emodin inhibited TPA-induced degradation of inhibitor of kappaBα, nuclear translocation of p65, and NF-κB DNA-binding activity. Taken together, these results suggest that emodin inhibits the invasiveness of human cancer cells by suppressing MMP-9 expression through inhibiting AP-1 and NF-κB signaling pathways. © 2004 Elsevier Inc. All rights reserved.