A curcumin analog, GO-Y078, effectively inhibits angiogenesis through actin disorganization

Shunsuke Sugiyama, Yuki Yoshino, Sei Kuriyama, Masahiro Inoue, Keigo Komine, Kazunori Otsuka, Aki Kohyama, Hiroyuki Yamakoshi, Chikashi Ishioka, Masamitsu Tanaka, Yoshiharu Iwabuchi, Hiroyuki Shibata

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Background: The inhibition of angiogenesis is a theoretically ideal chemotherapy for cancer, but there remains room for improvement. Most inhibitors of angiogenesis approved to date target vascular endothelial growth factors (VEGFs); however, VEGFs are only one of the many classes of participant in tumor angiogenesis. Because tumor angiogenesis is orchestrated by many components, including growth factors, signal transducers, and effectors, its regulation exhibits redundancy. Curcumin can associate with many proteins, and it reportedly inhibits tumor angiogenesis. Objective: We investigated the ability of a new curcumin analog, GO-Y078, to inhibit tumor angiogenesis. Results: GO-Y078 inhibited human umbilical vascular endothelial cell sprouting. GO-Y078 also induced complete anoikis in vascular endothelial cells. Moreover, GO-Y078 suppressed the migration and invasion of vascular endothelial cells into extracellular matrix proteins. However, expression analysis revealed that GO-Y078 did not suppress molecules involved in VEGF signaling. Rather, GOY078 induced actin disorganization, dissociation of vinculin from actin, and destruction of focal adhesion, resulting in the inhibition of vascular endothelial cell mobility. GO-Y078 also suppressed in-vivo vasculogenesis in Xenopus laevis tadpoles. Conclusion: Actin organization is a common effecter related to vascular endothelial cell mobility in angiogenesis. We demonstrated that GO-Y078 inhibits angiogenesis through actin disorganization.

Original languageEnglish
Pages (from-to)633-647
Number of pages15
JournalAnti-Cancer Agents in Medicinal Chemistry
Volume16
Issue number5
DOIs
Publication statusPublished - 2016 May 1

Keywords

  • Actin
  • Angiogenesis inhibitors
  • Curcumin
  • Endothelial cells
  • Vascular endothelial growth factor a

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Cancer Research

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