Angiogenesis is a complicated pathological
process and plays an
important role in modulating tumor development. Flavonoids, sharing
the basic functional group with estrogen, have been utilized as chemopreventive
agents to inhibit endothelial cell angiogenesis and also suppress
tumor cell proliferation. Ononin, also referred to as formononetin-7-O-β-d-glucoside, is one of the bioactive
chemicals found within many functional food or plants. The anticancer
functions of ononin have been reported both in vitro and in vivo. However, the anti-angiogenetic properties
of ononin have not been reported. The possible efficacies of ononin
against angiogenesis was verified in cultured endothelial cells. Ononin
suppressed vascular endothelial growth factor (VEGF)-induced HUVEC
migration, invasion. and tube formation activity after 48 h. The apoptosis
rate and specific markers, i.e., Bax/Bc-2 ratio, cleaved caspase 3/9
(Cl-caspase 3/9), and cytochrome c (Cyto c), were enhanced in the
ononin-treated group. On the other hand, the protein expressions levels
of hypoxia-inducible factor 1α (HIF-1α), mitogen-activated
protein kinase kinase (MEK)/extracellular signal-regulated kinase
(ERK), and vascular endothelial growth factor receptor 2 (VEGFR2)
were restricted after ononin treatment for 2 days in VEGF-pretreated
endothelial cells. In summary, ononin acts as a candidate for angiogenetic-related
disease prevention and treatment.
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