Anti-Angiogenic Activity of Quercetin and its Derivatives

Natural polyphenolic compounds have attractive consideration for their cancer preventive effect. As their anti-cancer effect, inhibitory effect on angiogenesis would be important. Recently, it has been shown that quercetin has anti-angiogenic activity and is a potent anti-cancer agent. However, the activity of its glycosylated forms and related derivatives has not been investigated yet. In this study, we examined the effect of glycosylated quercetin on angiogenesis. Interestingly, quercetin 3-O-β-D-glucose (isoquercitrin) showed the strongest inhibitory effect on an ex vivo angiogenesis assay, but quercetin 3-O-β-D-glucose-[1,6]-O-α-Lrhamnose (rutin) had no effect. Inhibitory effect of quercetin 7-O-β-D-glucose (quercimeritrin) was almost similar to that of quercetin. Furthermore, we compared the activity of acylated isoquercitrins (isoquercitrin cinnamate, dihydrocinnamate, p-coumarate, and 2-naphthalate). Consequently, anti-angiogenic activity of the isoquercitrin derivatives was weaker than that of isoquercitrin. The effects of quercetin and its derivatives on human umbilical endothelial cell (HUVEC) proliferation, HUVEC tube formation and chemotaxis assays were associated with their effects on the ex vivo angiogenesis assay.