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.