Anti-angiogenesis targeting
vascular endothelial growth factor receptor 2 (VEGFR2) has emerged as an important tool for
cancer treatment. In this study, we described a novel VEGFR2 inhibitor,
xanthatin, which inhibits
tumor angiogenesis and growth. The biochemical profiles of
xanthatin were investigated using
kinase assay, migration assay, tube formation,
Matrigel plug assay, western blot, immunofluorescence and human
tumor xenograft model.
Xanthatin significantly inhibited growth, migration and tube formation of human umbilical vascular endothelial cell as well as inhibited
vascular endothelial growth factor (
VEGF)-stimulated angiogenesis. In addition, it inhibited
VEGF-induced phosphorylation of VEGFR2 and its downstream signaling regulator. Moreover,
xanthatin directly inhibit proliferation of
breast cancer cells MDA-MB-231.
Oral administration of
xanthatin could markedly inhibit human
tumor xenograft growth and decreased microvessel densities (MVD) in
tumor sections. Taken together, these preclinical evaluations suggest that
xanthatin inhibits angiogenesis and may be a promising anticancer
drug candidate.