Zerumbone inhibits tumor angiogenesis via NF-κB in gastric cancer

Zerumbone derived from a subtropical ginger, Zingiber zerumbet Smith, was previously reported to have antitumor growth and anti-inflammatory properties in some types of cancer. However, the effects of zerumbone against cancer angiogenesis have not been fully elucidated. In this study, we clarified the role of zerumbone in gastric cancer angiogenesis. We examined the expression of vascular endothelial growth factor (VEGF) in gastric cancer cell lines both in the basal state and following zerumbone treatment by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA). Changes in gastric cancer cell proliferation in response to zerumbone treatment were measured by WST-1 assay. Additionally, the effects of zerumbone on NF-κB activity were examined in AGS cells. Finally, the effects of zerumbone on angiogenesis in AGS cells were measured by in vitro angiogenesis assay in which human umbilical vein endothelial cells (HUVECs) and fibroblasts were cocultured with AGS cells. Among the 6 gastric cancer cell lines tested, AGS cells exhibited the highest expression of VEGF. Cell proliferation, VEGF expression and NF-κB activity in AGS cells were all significantly inhibited by zerumbone. Moreover, the tube formation area of HUVECs was increased by coculture with AGS cells, and this effect was inhibited by zerumbone. Both VEGF expression and NF-κB activity in AGS cells were reduced by treatment with zerumbone, thereby inhibiting angiogenesis. Thus, zerumbone may become a new anti-angiogenic and antitumor drug in the treatment of gastric cancer.