title: 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.affiliation: Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea.
authors.forename: Mi Suk
authors.initials: MS
authors.lastname: Kim
authors.forename: Myung Jin
authors.initials: MJ
authors.lastname: Park
authors.forename: So Jeong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Chang Hun
authors.initials: CH
authors.lastname: Lee
authors.forename: Heon
authors.initials: H
authors.lastname: Yoo
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Shin
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Song
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004642:Emodin / Q000494:pharmacology* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D004791:Enzyme Inhibitors; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D018808:Transcription Factor AP-1; D006820:Hyaluronic Acid; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004642:Emodin