title: Interaction between 8-hydroxyquinoline ruthenium(II) complexes and basic fibroblast growth factors (bFGF): inhibiting angiogenesis and tumor growth through ERK and AKT signaling pathways.
abstract: Angiogenesis is crucial for tumor growth. Thus, inhibiting angiogenesis represents a promising avenue for preventing tumor growth. This study investigated the anti-angiogenesis and anti-tumor effects of 8-hydroxyquinoline ruthenium(II) complexes [Ru(bpy)2(8-HQ)](+) (BQ) and [Ru(phen)2(8-HQ)](+) (PQ). The results showed that both compounds, especially PQ, suppressed the proliferation, migration, invasion, tube formation and microvessel growth of endothelial cells in vitro. PQ also inhibited tumor growth of human hepatocellular liver carcinoma cells (HepG2) in a mouse xenograft tumor model in vivo. To understand the mechanisms of how ruthenium(II) complexes disrupt bFGF-induced angiogenesis and tumor growth, we have shown that (1) both compounds can interfere with the binding of bFGF to its cell surface receptors, thereby suppressing activation of bFGF-mediated signaling cascades; (2) PQ can induce tumor cell apoptosis. These effects might inhibit angiogenesis and tumor cell proliferation in tumor tissue. Taken together, our findings reveal that 8-hydroxyquinoline ruthenium(II) complexes are specific inhibitors of bFGF-mediated angiogenesis, and may be a viable drug candidate in anti-angiogenesis and anti-tumor therapies.
authors: Department of Chemistry, Jinan University, Guangzhou 510632, P. R. China. 972601962@qq.com tliuliu@jnu.edu.cn.
authors: Licong
authors: L
authors: Yang
authors: Jingnan
authors: J
authors: Zhang
authors: Chuan
authors: C
authors: Wang
authors: Xiuying
authors: X
authors: Qin
authors: Qianqian
authors: Q
authors: Yu
authors: Yanhui
authors: Y
authors: Zhou
authors: Jie
authors: J
authors: Liu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015125:Oxyquinoline / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D016222:Fibroblast Growth Factor 2; D015125:Oxyquinoline; D012428:Ruthenium; D051057:Proto-Oncogene Proteins c-akt