Emodin suppresses hyaluronic acid-induced MMP-9 secretion and invasion of glioma cells.

Abstract

Emodin, an inhibitor of protein tyrosine kinase, possesses antiviral, immunosuppressive, anti-inflammatory and anticancer effects. In the present study, we investigated the effect of emodin on the hyaluronic acid (HA)-induced invasion of human glioma cells. Emodin significantly inhibited the HA-induced invasion through a Matrigel coated chamber, secretion of matrix metalloproteinase (MMP)-2, and HA-induced secretion of MMP-9 in glioma cells. To investigate the possible mechanisms involved in these events, we performed Western blot analysis using phospho-specific antibodies, and found that emodin inhibited phosphorylation of focal adhesion kinase (FAK), extracellular regulated protein kinase (ERK) 1/2 and Akt/PKB; emodin also suppressed the transcriptional activity of two transcription factors, activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB), in glioma cells. In addition, oral administration of emodin suppressed in vivo MMP secretion by glioma tumors in nude mice. Taken together, our results indicate that emodin can effectively inhibit HA-induced MMP secretion and invasion of glioma through inhibition of FAK, ERK1/2 and Akt/PKB activation and partial inhibition of AP-1 and NF-kappaB transcriptional activities. Consequently, these results provide important insights into emodin as an anti-invasive agent for the therapy of human glioma.

• Authors: Mi Suk Kim, Myung Jin Park, So Jeong Kim, Chang Hun Lee, Heon Yoo, Sang Hoon Shin, Eun Sook Song, Seung Hoon Lee
• Journal: International journal of oncology (Int J Oncol) Vol. 27 Issue 3 Pg. 839-46 (Sep 2005) ISSN: 1019-6439 [Print] Greece
• PMID: 16077936 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• NF-kappa B
• Proto-Oncogene Proteins
• Transcription Factor AP-1
• Hyaluronic Acid
• Protein-Tyrosine Kinases
• Focal Adhesion Kinase 1
• Focal Adhesion Protein-Tyrosine Kinases
• PTK2 protein, human
• Ptk2 protein, mouse
• AKT1 protein, human
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinases
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• Emodin

Topics

• Animals
• Blotting, Western
• Cell Line, Tumor
• Cell Movement (drug effects)
• Dose-Response Relationship, Drug
• Emodin (pharmacology, therapeutic use)
• Enzyme Inhibitors (pharmacology)
• Focal Adhesion Kinase 1
• Focal Adhesion Protein-Tyrosine Kinases
• Gene Expression Regulation, Enzymologic (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Glioma (drug therapy, metabolism, pathology)
• Humans
• Hyaluronic Acid (pharmacology)
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• Neoplasm Invasiveness
• Phosphorylation (drug effects)
• Protein Binding (drug effects)
• Protein Serine-Threonine Kinases (metabolism)
• Protein-Tyrosine Kinases (metabolism)
• Proto-Oncogene Proteins (metabolism)
• Proto-Oncogene Proteins c-akt
• Reverse Transcriptase Polymerase Chain Reaction
• Time Factors
• Transcription Factor AP-1 (metabolism)
• Xenograft Model Antitumor Assays (methods)