title: Nobiletin inhibits invasion and migration of human nasopharyngeal carcinoma cell lines by involving ERK1/2 and transcriptional inhibition of MMP-2.
abstract: OBJECTIVE
  Nasopharyngeal carcinoma (NPC) is known for its high incidence of neck lymph node metastasis, which represents poor prognosis. Nobiletin is a citrus polymethoxyflavonoid that suppresses tumor growth and metastasis, both of which depend on angiogenesis in previous studies. However, the effect of Nobiletin on human NPC cells metastasis has not been clearly clarified.
  
  
  METHODS
  In this study, we determine the effects of Nobiletin on the migration and invasion in NPC cells.
  
  
  RESULTS
  Nobiletin significantly inhibited migration/invasion capacities of HONE-1 and NPC-BM cell lines. The results of gelatin zymography and western blotting revealed that the activities and protein levels of the MMP-2 were inhibited by Nobiletin. Nobiletin also showed that inhibits phosphorylation of ERK1/2. Tests of the real-time PCR and promoter assays evaluated the inhibitory effects of Nobiletin on MMP-2 expression in human NPC cells. Nobiletin inhibits MMP-2 expression, up-regulating tissue inhibitor of metalloproteinase-2 and down-regulation of the transcription factors of NF-κB and activator protein 1 (AP-1) signaling pathways. Finally, an administration of Nobiletin effectively suppressed the tumor formation and metastasis in the NPC xenograft model in vivo.
  
  
  CONCLUSIONS
  Nobiletin may have potential use as a chemo-preventive agent against nasopharyngeal cancer metastasis.
authors.affiliation: Changhua Christian Hospital, Department of Pharmacy , Changhua 500, Taiwan , Republic of China.
authors.forename: Su-Yu
authors.initials: SY
authors.lastname: Chien
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Hsieh
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Chen
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.forename: Mu-Kuan
authors.initials: MK
authors.lastname: Chen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D047309:Flavones / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010766:Phosphorylation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047309:Flavones; C008661:nobiletin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020778:Matrix Metalloproteinase 2
keywords: MMP-2; human nasopharyngeal carcinoma; invasion; migration; nobiletin