title: Kaempferol reduces matrix metalloproteinase-2 expression by down-regulating ERK1/2 and the activator protein-1 signaling pathways in oral cancer cells.
abstract: BACKGROUND
  Kaempferol has been proposed as a potential drug for cancer chemoprevention and treatment because it is a natural polyphenol contained in plant-based foods. Recent studies have demonstrated that kaempferol protects against cardiovascular disease and cancer. Based on this finding, we investigated the mechanisms by which kaempferol produces the anti-metastatic effect in human tongue squamous cell carcinoma SCC4 cells.
  
  
  RESULTS
  In this study, we provided molecular evidence associated with the anti-metastatic effect of kaempferol by demonstrating a substantial suppression of SCC4 cell migration and invasion. This effect was associated with reduced expressions of MMP-2 and TIMP-2 mRNA and protein levels. Analysis of the transcriptional regulation indicated that kaempferol inhibited MMP-2 transcription by suppressing c-Jun activity. Kaempferol also produced an inhibitory effect on the phosphorylation of ERK1/2.
  
  
  CONCLUSIONS
  These findings provide new insights into the molecular mechanisms involved in the anti-metastatic effect of kaempferol, and are valuable in the prevention of oral cancer metastasis.
authors.affiliation: Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan ; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Chiao-Wen
authors.initials: CW
authors.lastname: Lin
authors.forename: Pei-Ni
authors.initials: PN
authors.lastname: Chen
authors.forename: Mu-Kuan
authors.initials: MK
authors.lastname: Chen
authors.forename: Wei-En
authors.initials: WE
authors.lastname: Yang
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004273:DNA, Neoplasm / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D044949:Kaempferols / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D002070:Butadienes; D004273:DNA, Neoplasm; D044949:Kaempferols; D061965:Matrix Metalloproteinase Inhibitors; D009570:Nitriles; D012333:RNA, Messenger; C560823:TIMP2 protein, human; D018808:Transcription Factor AP-1; C113580:U 0126; D019716:Tissue Inhibitor of Metalloproteinase-2; C006552:kaempferol; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2