title: Suppressive function of low-dose deguelin on the invasion of oral cancer cells by downregulating tumor necrosis factor alpha-induced nuclear factor-kappa B signaling.
abstract: Deguelin has both antiproliferation and antimetastasis activities. However, high-dose deguelin elicits many undesired side effects. The purpose of this study was to investigate whether the low-dose deguelin can prevent the metastasis of oral cancer.
  
  
  
  The dose effects of deguelin on metastasis of oral cancer cells were analyzed by in vitro invasion assay and an orthotropic xenograft mouse model. The involvement of tumor necrosis factor alpha (TNF-α)-induced nuclear factor-kappa B (NF-κB) signaling was examined by Western blot and reporter assay.
  
  
  
  Low-dose deguelin, which has minimal cytotoxicity, significantly inhibited the invasion and migration of oral cancer cells. These inhibitory effects of low-dose deguelin were mediated by suppressing TNF-α-induced activation of IκB kinase leading to the inhibition of IκB phosphorylation, NF-κB transcriptional activity, and matrix metalloproteinase-2 (MMP2) expression. The low-dose deguelin treatment significantly inhibited tumor growth and invasion without systemic toxicity.
  
  
  
  The low-dose deguelin suppressed the invasion and migration of oral cancer by downregulating TNF-α-induced NF-κB signaling. © 2015 Wiley Periodicals, Inc. Head Neck 38: E524-E534, 2016.
authors.affiliation: Department of Genome Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.|Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Yu-Peng
authors.initials: YP
authors.lastname: Liu
authors.affiliation: Department of Veterinary Medicine, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan.
authors.forename: Jih-Jong
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Tsung-Ching
authors.initials: TC
authors.lastname: Lai
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Chien-Hsin
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Hsiao
authors.affiliation: Graduate School of Biomedical Sciences, University of Massachusetts Medical School, Worcester, Massachusetts.
authors.forename: Po-Shen
authors.initials: PS
authors.lastname: Chen
authors.affiliation: Institute of Pharmacology, National Cheng-Kung University, Tainan, Taiwan.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Liu
authors.affiliation: Institute of Clinical Dentistry, School of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Hong
authors.affiliation: Institute of Clinical Dentistry, School of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Se-Kwan
authors.initials: SK
authors.lastname: Lin
authors.affiliation: Institute of Clinical Dentistry, School of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Mark-Yen
authors.initials: MY
authors.lastname: Ping Kuo
authors.affiliation: Institute of Clinical Medicine, National Cheng-Kung University, Tainan, Taiwan.
authors.forename: Pei-Jung
authors.initials: PJ
authors.lastname: Lu
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D012402:Rotenone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D012402:Rotenone; D020778:Matrix Metalloproteinase 2; C107676:deguelin
keywords: deguelin; invasion; matrix metalloproteinase-2 (MMP2); nuclear factor-kappa B (NF-κB); oral cancer