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

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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 2006

All Science Journal Classification (ASJC) codes

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

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    Aoki, S., Cho, S. H., Ono, M., Kuwano, T., Nakao, S., Kuwano, M., Nakagawa, S., Gao, J. Q., 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, 17(3), 269-278. https://doi.org/10.1097/00001813-200603000-00005