Institute for World Health Development, Mukogawa Women's University, Hyogo, Japan.
Mol Nutr Food Res. 2011 Nov;55(11):1730-4. doi: 10.1002/mnfr.201100098. Epub 2011 Sep 21.
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.
血管生成是癌症预防和治疗的一个有前途的靶点。本研究旨在确定瓜栗（Gnetum gnemon L.）种仁提取物及其白藜芦醇衍生物成分（如 Gnetin C（GC）、Gnetin L（GL）、Gnemonside A（GMA）、Gnemonside C（GMC）和 Gnemonside D（GMD））的抗血管生成作用。瓜栗种仁的乙醇提取物（EEMS）和两种 Gnetin 显著抑制了血管内皮生长因子和碱性成纤维细胞生长因子刺激的人脐静脉内皮细胞（HUVEC）的增殖和管形成。GC 和 GL 的抑制作用比白藜芦醇强得多。GMC 和 GMD 仅抑制增殖，而 GMA 对两种内皮细胞功能几乎没有影响。EEMS 和 GC 还降低了形成管的 HUVEC 的细胞活力，伴随 ERK1/2 失活，并抑制了 HUVEC 的迁移。此外，EEMS 的饮食摄入显著抑制了小鼠背部气囊试验中的肿瘤血管生成。总之，我们发现 EEMS 及其白藜芦醇衍生物，特别是 GC，抑制多种与血管生成相关的内皮细胞功能和/或肿瘤血管生成，表明瓜栗种子和天然白藜芦醇衍生物可能可用于癌症的预防和治疗。
