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A new human in vitro anti-angiogenesis assay was established and applied to identify novel angiopreventive agents. Subsequently, two chemopreventive compounds, xanthohumol (XN) from Humulus lupulus L. (hop) and sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables (Brassicaceae), were selected for detailed investigation of their angiopreventive potential and mechanisms involved in the inhibition of angiogenesis. Representative targets included effects at the transcriptional levels of pro-angiogenic factors, anti-gelatinolytic and anti-endothelial activity. In vivo, XN was shown to exhibit a strong anti-tumour potency on human breast cancer xenografts mediated by the inhibition of tumour-induced angiogenesis.These findings strongly suggest that XN and SFN represent attractive chemopreventive lead structures possessing a remarkable potential to prevent tumour development.