Consumption of a plant-based diet can prevent the development and progression of chronic diseases that are associated with extensive neovascularization; however, little is known about the mechanisms. To determine whether prevention might be associated with dietary-derived angiogenesis inhibitors, we have fractionated urine of healthy human subjects consuming a plant-based diet and examined the fractions for their abilities to inhibit the proliferation of vascular endothelial cells. Using gas chromatography-mass spectrometry, we showed that one of the most potent fractions contained several isoflavonoids, which we subsequently synthesized. Of all synthetic compounds, the isoflavonoid genistein was the most potent and inhibited endothelial cell proliferation and in vitro angiogenesis at concentrations giving half-maximal inhibition of 5 and 150 FzM, respectively. As we have previously demonstrated, genistein concentrations in urine of subjects consuming a plant-based diet are in the micromolar range, while those ofsubjects consuming a traditional Western diet are lower by a factor of >30. The high excretion of genistein in urine of vegetarians and our present results suggest that genistein may contribute to the preventive effect of a plantbased diet on chronic diseases, including solid tumors, by inhibiting neovascularization. Thus, genistein may represent a member of a new class of dietary-derived anti-angiogenic compounds.Angiogenesis, the generation of new capillaries, is virtually absent in the healthy adult organism and is restricted to a few conditions including wound healing and the formation of corpus luteum, endometrium, and placenta. These conditions of normal angiogenesis represent ordered, tightly regulated, and self-limited processes (1) and are probably the result of a well-balanced activity of angiogenesis inhibitors and stimulators. Otherwise, angiogenesis is virtually nonexistent, and of all vascular endothelial cells present in the organism, <0

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