title: Zerumbone inhibits angiogenesis by blocking NF-κB activity in pancreatic cancer.
abstract: OBJECTIVE
  Because angiogenesis is essential for tumor growth and metastasis, the development of antiangiogenic agents is an urgent issue in cancer treatment. Zerumbone, a component of subtropical ginger, has been shown to exhibit anticancer activities in various cancer cells; however, little is known about its biological mechanisms against angiogenesis in pancreatic cancer (PaCa). Here, we evaluated the effects of zerumbone on PaCa angiogenesis.
  
  
  METHODS
  The cytotoxicity of zerumbone in PaCa was measured using premix WST-1 cell proliferation assays. The influence of zerumbone on the angiogenic factors vascular endothelial growth factor and interleukin 8 was measured using the reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assays. Changes in nuclear factor-κB (NF-κB) activities were measured using NF-κB transcription factor assays. We also examined the effects of zerumbone on PaCa-induced angiogenesis using angiogenesis assays.
  
  
  RESULTS
  Zerumbone inhibited mRNA expression and protein secretion of angiogenic factors and NF-κB activity. Tube formation in human umbilical vein endothelial cells was enhanced by coculture with PaCa cells, and these enhancements were significantly inhibited by zerumbone treatment.
  
  
  CONCLUSIONS
  Zerumbone blocked the PaCa-associated angiogenesis through the inhibition of NF-κB and NF-κB-dependent proangiogenic gene products.
authors.affiliation: From the Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Shamoto
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shibata
authors.forename: Ken
authors.initials: K
authors.lastname: Tsuboi
authors.forename: Takaya
authors.initials: T
authors.lastname: Nagasaki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Funahashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Okada
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Takeyama
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012717:Sesquiterpenes / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D012717:Sesquiterpenes; D042461:Vascular Endothelial Growth Factor A; C403304:zerumbone