title: 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 [RuIII(N2O2)Cl2]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.
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Chemical Biology Centre and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P.R. China.
authors.forename: Wai-Lun
authors.initials: WL
authors.lastname: Kwong
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Chemical Biology Centre and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P.R. China.
authors.forename: Kar-Yee
authors.initials: KY
authors.lastname: Lam
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Chemical Biology Centre and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P.R. China.
authors.forename: Chun-Nam
authors.initials: CN
authors.lastname: Lok
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Chemical Biology Centre and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P.R. China.
authors.forename: Yau-Tsz
authors.initials: YT
authors.lastname: Lai
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Chemical Biology Centre and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P.R. China.
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Lee
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Chemical Biology Centre and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P.R. China. cmche@hku.hk.|HKU Shenzhen Institute of Research and Innovation, Shenzen 518053, P.R. China. cmche@hku.hk.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Che
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D047028:Macrocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015027:Zebrafish
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D047028:Macrocyclic Compounds; D012428:Ruthenium; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: VEGFRs; angiogenesis; anti-cancer; ruthenium