title: A Curcumin Analog, GO-Y078, Effectively Inhibits Angiogenesis through Actin Disorganization.
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.
  
  
  CONCLUSIONS
  Actin organization is a common effecter related to vascular endothelial cell mobility in angiogenesis. We demonstrated that GO-Y078 inhibits angiogenesis through actin disorganization.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Sugiyama
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yoshino
authors.forename: Sei
authors.initials: S
authors.lastname: Kuriyama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inoue
authors.forename: Keigo
authors.initials: K
authors.lastname: Komine
authors.forename: Kazunori
authors.initials: K
authors.lastname: Otsuka
authors.forename: Aki
authors.initials: A
authors.lastname: Kohyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamakoshi
authors.forename: Chikashi
authors.initials: C
authors.lastname: Ishioka
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Iwabuchi
authors.affiliation: Department of Clinical Oncology, Graduate School of Medicine, Akita University, Akita, Japan. hiroyuki@med.akita-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shibata
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D000199:Actins; C000612955:GO-Y078; D042442:Vascular Endothelial Growth Factors; D003474:Curcumin