Zerumbone Inhibits Angiogenesis by Blocking NF-JB Activity in Pancreatic Cancer

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-B (NF-B) activities were measured using NF-B 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-B 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-B and NF-B-dependent proangiogenic gene products.