Bastadin 6, a spongean brominated tyrosine derivative, inhibits tumor angiogenesis by inducing selective apoptosis to endothelial cells

Shunji Aoki, Seok Hwan Cho, Mayumi Ono, Takashi Kuwano, shintaro nakao, Michihiko Kuwano, Shinsaku Nakagawa, Jian Qing Gao, Tadanori Mayumi, Masabumi Shibuya, Motomasa Kobayashi

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Bastadin 6, a macrocyclic tetramer of a brominated tyrosine derivative, was isolated from a marine sponge and its anti-angiogenic activity was evaluated. Bastadin 6 was found to inhibit vascular endothelial growth factor (VEGF)- or basic fibroblast growth factor (bFGF)-dependent proliferation (IC50 = 0.052 μmol/l) of human umbilical vein endothelial cells (HUVECs) 20- to 100-fold selectively in comparison with normal fibroblast (3Y1) or several tumor cells (KB3-1, K562 and Neuro2A). Bastadin 6 also inhibited VEGF- or bFGF-induced tubular formation (0.1 μmol/l, 6 h treatment) and VEGF-induced migration (1 μmol/l, 4 h treatment) of HUVECs. Moreover, bastadin 6 almost completely blocked VEGF- or bFGF-induced in vivo neovascularization in the mice corneal assay and suppressed growth of s.c. inoculated A431 solid tumor in nude mice (100 mg/kg, i.p.). Bastadin 6 induced cell death of HUVECs with an apoptotic phenotype, whereas it showed no effect on the VEGF-induced auto-phosphorylation of VEGF receptors Flt-1 and KDR/Flk-1. These results suggest that the anti-angiogenic effect of bastadin 6 is closely related to selective induction activity of apoptosis against endothelial cells.

Original languageEnglish
Pages (from-to)269-278
Number of pages10
JournalAnti-Cancer Drugs
Volume17
Issue number3
DOIs
Publication statusPublished - Mar 1 2006

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Tyrosine
Endothelial Cells
Vascular Endothelial Growth Factor A
Apoptosis
Human Umbilical Vein Endothelial Cells
Fibroblast Growth Factor 2
Neoplasms
Vascular Endothelial Growth Factor Receptor-1
Porifera
Nude Mice
Inhibitory Concentration 50
bastadin 6
Cell Death
Fibroblasts
Phosphorylation
Phenotype
Growth

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research

Cite this

Bastadin 6, a spongean brominated tyrosine derivative, inhibits tumor angiogenesis by inducing selective apoptosis to endothelial cells. / Aoki, Shunji; Cho, Seok Hwan; Ono, Mayumi; Kuwano, Takashi; nakao, shintaro; Kuwano, Michihiko; Nakagawa, Shinsaku; Gao, Jian Qing; Mayumi, Tadanori; Shibuya, Masabumi; Kobayashi, Motomasa.

In: Anti-Cancer Drugs, Vol. 17, No. 3, 01.03.2006, p. 269-278.

Research output: Contribution to journalArticle

Aoki, S, Cho, SH, Ono, M, Kuwano, T, nakao, S, Kuwano, M, Nakagawa, S, Gao, JQ, Mayumi, T, Shibuya, M & Kobayashi, M 2006, 'Bastadin 6, a spongean brominated tyrosine derivative, inhibits tumor angiogenesis by inducing selective apoptosis to endothelial cells', Anti-Cancer Drugs, vol. 17, no. 3, pp. 269-278. https://doi.org/10.1097/00001813-200603000-00005
Aoki, Shunji ; Cho, Seok Hwan ; Ono, Mayumi ; Kuwano, Takashi ; nakao, shintaro ; Kuwano, Michihiko ; Nakagawa, Shinsaku ; Gao, Jian Qing ; Mayumi, Tadanori ; Shibuya, Masabumi ; Kobayashi, Motomasa. / Bastadin 6, a spongean brominated tyrosine derivative, inhibits tumor angiogenesis by inducing selective apoptosis to endothelial cells. In: Anti-Cancer Drugs. 2006 ; Vol. 17, No. 3. pp. 269-278.
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