Zerumbone inhibits angiogenesis by blocking NF-κB activity in pancreatic cancer

Pancreas. 2014 Apr;43(3):396-404. doi: 10.1097/MPA.0000000000000039.


Objectives: 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.

MeSH terms

  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Coculture Techniques
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation, Neoplastic / drug effects
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / physiology
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • NF-kappa B / metabolism*
  • Neovascularization, Pathologic / prevention & control*
  • Neovascularization, Physiologic / drug effects
  • Pancreatic Neoplasms / blood supply
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sesquiterpenes / pharmacology*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism


  • Interleukin-8
  • NF-kappa B
  • Sesquiterpenes
  • Vascular Endothelial Growth Factor A
  • zerumbone