Inhibition of in vivo angiogenesis by N-β-alanyl-5- S-glutathionyl-3,4-dihydroxyphenylalanine

N-β-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 prolifera...

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Veröffentlicht in:European journal of pharmacology 2006-06, Vol.539 (3), p.151-157
Hauptverfasser: Nishikawa, Takeshi, Akiyama, Nobuko, Kunimasa, Kazuhiro, Oikawa, Tsutomu, Ishizuka, Masaaki, Tsujimoto, Masafumi, Natori, Shunji
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container_issue 3
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container_title European journal of pharmacology
container_volume 539
creator Nishikawa, Takeshi
Akiyama, Nobuko
Kunimasa, Kazuhiro
Oikawa, Tsutomu
Ishizuka, Masaaki
Tsujimoto, Masafumi
Natori, Shunji
description N-β-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.
doi_str_mv 10.1016/j.ejphar.2006.03.084
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subjects 5-S-GAD
Angiogenesis
Angiogenesis Inhibitors - pharmacology
Angiogenesis Inhibitors - therapeutic use
Animals
Antiangiogenic agent
Biological and medical sciences
Cell Line, Tumor
Chick Embryo
Dihydroxyphenylalanine - analogs & derivatives
Dihydroxyphenylalanine - pharmacology
Dihydroxyphenylalanine - therapeutic use
Dose-Response Relationship, Drug
Female
Glutathione - analogs & derivatives
Glutathione - pharmacology
Glutathione - therapeutic use
Humans
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Neovascularization, Pathologic - drug therapy
Neovascularization, Pathologic - pathology
Neovascularization, Physiologic - drug effects
Neovascularization, Physiologic - physiology
Pharmacology. Drug treatments
Tumor therapy
Xenograft Model Antitumor Assays - methods
title Inhibition of in vivo angiogenesis by N-β-alanyl-5- S-glutathionyl-3,4-dihydroxyphenylalanine
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