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

Abstract

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.

• Authors: Tomoya Shamoto, Yoichi Matsuo, Takahiro Shibata, Ken Tsuboi, Takaya Nagasaki, Hiroki Takahashi, Hitoshi Funahashi, Yuji Okada, Hiromitsu Takeyama
• Journal: Pancreas (Pancreas) Vol. 43 Issue 3 Pg. 396-404 (Apr 2014) ISSN: 1536-4828 [Electronic] United States
• PMID: 24622069 (Publication Type: Journal Article)

Chemical References

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

Topics

• 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, physiology)
• Humans
• Interleukin-8 (genetics, metabolism)
• NF-kappa B (metabolism)
• Neovascularization, Pathologic (prevention & control)
• Neovascularization, Physiologic (drug effects)
• Pancreatic Neoplasms (blood supply, genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Sesquiterpenes (pharmacology)
• Vascular Endothelial Growth Factor A (genetics, metabolism)