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

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.
AuthorsMi Suk Kim, Myung Jin Park, So Jeong Kim, Chang Hun Lee, Heon Yoo, Sang Hoon Shin, Eun Sook Song, Seung Hoon Lee
JournalInternational journal of oncology (Int J Oncol) Vol. 27 Issue 3 Pg. 839-46 (Sep 2005) ISSN: 1019-6439 [Print] Greece
PMID16077936 (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
  • 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, secretion)
  • 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)

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