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.