title: Tricetin suppresses the migration/invasion of human glioblastoma multiforme cells by inhibiting matrix metalloproteinase-2 through modulation of the expression and transcriptional activity of specificity protein 1.
abstract: OBJECTIVE
  Glioblastoma multiforme (GBM) is a severely invasive tumor that can be fatal because it is difficult to treat. Tricetin, a natural flavonoid, was demonstrated to inhibit the growth of various cancers, but the effect of tricetin on cancer motility is largely unknown.
  
  
  METHODS
  In the present study, we examined the anti-invasive properties of tricetin in huwman GBM cells.
  
  
  RESULTS
  Our results showed that tricetin inhibited the migration/invasion of two GBM cell lines. We found that tricetin inhibited MMP-2 expression in the GBM cells. Real-time polymerase chain reaction and promoter activity assays indicated that tricetin inhibited MMP-2 expression at the transcriptional level. Such inhibitory effects were associated with the suppression of specificity protein-1 (SP-1) DNA-binding activity. An examination of clinical samples revealed a positive correlation between SP-1 and MMP-2 in glioma specimens, and higher expression levels were correlated with a worse probability of survival. Moreover, blocking the extracellular signal-regulated kinase (ERK) pathway also inhibited MMP-2-mediated cell motility, and further enhanced the anti-invasive ability of tricetin in GBM cells.
  
  
  CONCLUSIONS
  SP-1 is an important target of tricetin for suppressing MMP-2-mediated cell motility in GBM cells, and a combination of tricetin and an ERK inhibitor may be a good strategy for preventing GBM invasion.
authors.affiliation: a 1 Chung Shan Medical University, Institute of Medicine , Taichung, Taiwan.
authors.forename: Rockey
authors.initials: R
authors.lastname: Chao
authors.affiliation: b 2 Taipei Medical University, Wan Fang Hospital, Department of Internal Medicine , Taipei, Taiwan.
authors.forename: Jyh-Ming
authors.initials: JM
authors.lastname: Chow
authors.affiliation: c 3 Chung Shan Medical University, School of Medicine, Department of Biochemistry , Taichung, Taiwan.
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Hsieh
authors.affiliation: d 4 Genomics Research Center, Academia Sinica , Taipei, Taiwan.|e 5 National Taiwan University, Graduate Institute of Toxicology, College of Medicine , Taipei, Taiwan.
authors.forename: Chi-Kuan
authors.initials: CK
authors.lastname: Chen
authors.affiliation: f 6 Taipei Medical University, Wan Fang Hospital, Department of Urology , Taipei, Taiwan.
authors.forename: Wei-Jiunn
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: g 7 Ludwig-Maximilians University, Department of Surgery, Experimental Surgery and Regenerative Medicine , Munich, Germany.
authors.forename: Feng-Koo
authors.initials: FK
authors.lastname: Hsieh
authors.affiliation: a 1 Chung Shan Medical University, Institute of Medicine , Taichung, Taiwan.
authors.forename: Nuo-Yi
authors.initials: NY
authors.lastname: Yu
authors.affiliation: a 1 Chung Shan Medical University, Institute of Medicine , Taichung, Taiwan.
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Chou
authors.affiliation: h 8 Taipei Medical University, Graduate Institute of Clinical Medicine , 250 Wu-Hsing Street, Taipei, Taiwan +886 2 2736 1661 ; +886 2 2739 0500 ; mhchien1976@gmail.com.
authors.forename: Chao-Wen
authors.initials: CW
authors.lastname: Cheng
authors.affiliation: a 1 Chung Shan Medical University, Institute of Medicine , Taichung, Taiwan.|i 9 Chung Shan Medical University Hospital, Department of Medical Research , Taichung, Taiwan.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.affiliation: h 8 Taipei Medical University, Graduate Institute of Clinical Medicine , 250 Wu-Hsing Street, Taipei, Taiwan +886 2 2736 1661 ; +886 2 2739 0500 ; mhchien1976@gmail.com.|j 10 Taipei Medical University, Wan Fang Hospital, Department of Medical Research , Taipei, Taiwan.
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Chien
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects* / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D060888:Real-Time Polymerase Chain Reaction; D016329:Sp1 Transcription Factor / Q000378:metabolism*
chemical_list: D002867:Chromones; D061965:Matrix Metalloproteinase Inhibitors; D016329:Sp1 Transcription Factor; C469689:tricetin; D020778:Matrix Metalloproteinase 2
keywords: extracellular signal-regulated kinase; glioblastoma; invasion; matrix metalloproteinases-2; specificity protein-1; tricetin