Anti-angiogenic activity of the flavonoid precursor 4-hydroxychalcone.

Angiogenesis, the growth of new blood vessels, is necessary for cancerous tumors to keep growing and spreading. Suppression of abnormal angiogenesis may provide therapeutic strategies for the treatment of angiogenesis-dependent disorders. In the present study, we describe the in vitro and in vivo anti-angiogenic activities of the flavonoid precursor 4-hydroxychalcone (Q797). This chalcone (22μg/ml) suppressed several steps of angiogenesis, including endothelial cell proliferation, migration and tube formation without showing any signs of cytotoxicity. Moreover, we found a selective effect on activated endothelial cells, in particular with resting endothelial cells and the human epithelial tumor cell lines (HeLa, MCF-7, A549). In addition, Q797 was able to modulate both vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (FGF)- induced phosphorylation of extracellular signal-regulated kinase (ERK)-1/-2 and Akt kinase. It did not influence the nuclear translocation of p65 subunit of the nuclear factor-κB (NF-κB) when human endothelial cells were stimulated with tumor necrosis factor (TNF)-α. Taken together this indicates that the Q797-mediated inhibition of in vitro angiogenic features of endothelial cells is most likely caused by suppression of growth factor pathways. The potent inhibitory effect of Q797 on bFGF-driven neovascularization was also demonstrated in vivo using the chick chorioallantoic membrane (CAM) assay. In summary, this chalcone could serve as a new leading structure in the discovery of new potent synthetic angiogenesis inhibitors.