(P05-020-20) Development of Functional Screens for Dietary Angiogenesis Inhibitors

Objectives: We sought to develop a workflow to evaluate the anti-angiogenic potential of dietary agents in a stringent, systemic manner: 1) in vitro inhibition of angiogenesis, 2) in vivo testing of normal angiogenesis inhibition, and 3) in vivo testing of tumor prevention.

Methods: We used a tiered workflow for assessment of anti-angiogenic potential of dietary compounds, beginning with cell culture methods, moving to high-throughput D. rerio angiogenesis modeling and finally mouse models of angiogenesis and tumor development to identify potent dietary agents which block tumor angiogenesis.

Results: We identified quercetin dihydrate as an orally available inhibitor of angiogenesis and our lead candidate for further evaluation for chemoprevention of angiogenesis. Quercetin blocked in vitro sprouting angiogenesis, and displayed a dose-dependent reduction in sprouting angiogenesis in the tail regeneration model in zebrafish. Finally, quercetin implanted at reported physiologic levels blocked blood vessel growth in mouse models of angiogenesis.

Conclusions: We describe a workflow for systematic evaluation of dietary compounds in increasing complexity models for stringent, systematic evaluation of angiogenesis inhibition. These multi-model approaches allow for filtering of pan-assay interference compounds (PAINS) prior to in vivo screening. This workflow identified quercetin as a potent inhibitor of angiogenesis which warrants further study for chemoprevention through diet.

Funding Sources: National Cancer Institute Division of Cancer Prevention, National Cancer Institute Center for Cancer Research