A Macrocyclic Ruthenium(III) Complex Inhibits Angiogenesis with Down‐Regulation of Vascular Endothelial Growth Factor Receptor‐2 and Suppresses Tumor Growth In Vivo

Abstract A macrocyclic ruthenium(III) complex [Ru III (N 2 O 2 )Cl 2 ]Cl ( Ru‐1 ) is reported as an inhibitor of angiogenesis and an anti‐tumor compound. The complex is relatively non‐cytotoxic towards endothelial and cancer cell lines in vitro, but specifically inhibited the processes of angiogenic endothelial cell tube formation and cancer cell invasion. Moreover, compared with known anti‐cancer ruthenium complexes, Ru‐1 is distinct in that it suppressed the expression of vascular endothelial growth factor receptor‐2 (VEGFR2), and the associated downstream signaling that is crucial to tumor angiogenesis. In addition, in vivo studies showed that Ru‐1 inhibited angiogenesis in a zebrafish model and suppressed tumor growth in nude mice bearing cancer xenografts.