Inhibitory effect of emodin on tumor invasion through suppression of activator protein-1 and nuclear factor-kappaB.
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-kappaB), 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 kappaBalpha, nuclear translocation of p65, and NF-kappaB 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-kappaB signaling pathways.
Huang
Qing
Q
Department of Community, Occupational, and Family Medicine, Faculty of Medicine, MD3, 16 Medical Drive, National University of Singapore, Singapore 117597, Singapore.
Shen
Han-Ming
HM
Ong
Choon-Nam
CN
D000970:Antineoplastic Agents / Q000494:pharmacology; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004642:Emodin / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D004642:Emodin; D013755:Tetradecanoylphorbol Acetate