Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 55, Issue 11, Pages 1730-1734Publisher
WILEY-BLACKWELL
DOI: 10.1002/mnfr.201100098
Keywords
Angiogenesis; Endothelial cells; Melinjo seeds; Resveratrol derivatives; Tube formation
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [21700773, 21500782]
- Yamada Bee Farm Grant for Honeybee Research
- Mukogawa Women's University
- Grants-in-Aid for Scientific Research [21700773, 21500782, 22500787] Funding Source: KAKEN
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Angiogenesis is a promising target for cancer prevention and treatment. This study aimed to determine the antiangiogenic effects of melinjo (Gnetum gnemon L.) seed extract and its resveratrol derivative components, such as gnetin C (GC), gnetin L (GL), gnemonoside A (GMA), gnemonoside C (GMC), and gnemonoside D (GMD). An ethanol extract of melinjo seeds (EEMS) and the two gnetins markedly inhibited the proliferation and tube formation of human umbilical vein endothelial cells (HUVEC) stimulated with vascular endothelial growth factor and basic fibroblast growth factor. The inhibitory effects of GC and GL were much stronger than those of resveratrol. GMC and GMD inhibited only proliferation, whereas GMA had almost no effect on the two endothelial cell functions. The EEMS and GC also reduced the cell viability of tube-forming HUVEC, with accompanying ERK1/2 inactivation, and suppressed the migration of HUVEC. Furthermore, dietary intake of EEMS significantly inhibited tumor angiogenesis in a mouse dorsal air sac assay. In conclusion, we found that the EEMS and its resveratrol derivatives, particularly GC, suppress multiple angiogenesis-related endothelial cell functions and/or tumor angiogenesis, indicating that the melinjo seeds and the natural resveratrol derivatives may be useful for cancer prevention and treatment.
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