A Catechol-Type Resveratrol Analog Manifests Antiangiogenic Action by Constructing an Efficient Catalytic Redox Cycle with Intracellular Copper Ions and NQO1.

Scope: As part of our research project to understand why dietary polyphenols with the catechol skeleton tend to exhibit cancer chemopreventive activity, a catechol-type resveratrol analog (3,4-dihydroxy-trans-stilbene [3,4-DHS]) was selected to probe its antiangiogenic effects and mechanisms.

Methods And Results: The antiangiogenic effects of 3,4-DHS on angiogenesis-related endothelial cell functions were examined, including migration, invasion, and tube formation, and in vivo angiogenesis on a chick chorioallantoic membrane assay. The potential molecular mechanisms for the suppression of cell migration by 3,4-DHS were analyzed using various specific inhibitors. 3,4-DHS was identified as a potent angiogenesis inhibitor by constructing an efficient catalytic redox cycle with intracellular copper ions and NAD(P)H quinone oxidoreductase I to generate reactive oxygen species and thereby downregulate matrix metalloproteinase-9.

Conclusion: This work provides further evidence that dietary catechols manifest antiangiogenic activity by virtue of their copper-dependent prooxidative instead of antioxidative role, and useful information for designing polyphenol-inspired angiogenesis inhibitors.