title: Inhibition of in vivo angiogenesis by N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine.
abstract: N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD), an antibacterial substance isolated from the flesh fly, inhibits human tumor growth in the nude mice model; however, the mechanism of its action is unclear. The in vivo antitumor effect includes the inhibition of tumor cell proliferation and suppression of angiogenesis. Angiogenesis is essential for tumor growth in vivo. In this study, we examined whether 5-S-GAD inhibits tumor cell-induced angiogenesis by performing the mouse dorsal air sac assay. We found that intraperitoneal administration of 5-S-GAD inhibited the angiogenesis induced by S180 mouse sarcoma cells. Furthermore, 5-S-GAD also inhibited vascular endothelial growth factor-induced angiogenesis in the Matrigel plug assay and embryonic angiogenesis in the chick embryo chorioallantoic membrane assay. However, 5-S-GAD did not show any effect on the proliferation, migration, and tube formation of vascular endothelial cells. These results provide the first evidence that a bioactive substance derived from the flesh fly has antiangiogenic activity in vivo, although the mechanisms involved could not be explained.
authors.affiliation: Natori Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Nobuko
authors.initials: N
authors.lastname: Akiyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kunimasa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Oikawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ishizuka
authors.forename: Masafumi
authors.initials: M
authors.lastname: Tsujimoto
authors.forename: Shunji
authors.initials: S
authors.lastname: Natori
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D045744:Cell Line, Tumor; D002642:Chick Embryo; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D020533:Angiogenesis Inhibitors; C100496:N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine; D004295:Dihydroxyphenylalanine; D005978:Glutathione