title: Resveratrol derivative-rich melinjo (Gnetum gnemon L.) seed extract suppresses multiple angiogenesis-related endothelial cell functions and tumor angiogenesis.
abstract: 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.
authors.affiliation: Institute for World Health Development, Mukogawa Women's University, Hyogo, Japan. kunimasa@mukogawa-u.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kunimasa
authors.forename: Toshiro
authors.initials: T
authors.lastname: Ohta
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tani
authors.forename: Eishin
authors.initials: E
authors.lastname: Kato
authors.forename: Ryoji
authors.initials: R
authors.lastname: Eguchi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kaji
authors.forename: Katsumi
authors.initials: K
authors.lastname: Ikeda
authors.forename: Hideki
authors.initials: H
authors.lastname: Mori
authors.forename: Mari
authors.initials: M
authors.lastname: Mori
authors.forename: Tomoki
authors.initials: T
authors.lastname: Tatefuji
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yamori
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D001681:Biological Assay; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D055808:Drug Discovery; D005260:Female; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology; D035684:Gnetum / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D000077185:Resveratrol; D012639:Seeds / Q000737:chemistry; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D005960:Glucosides; D010936:Plant Extracts; D013267:Stilbenes; D000077185:Resveratrol