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Interaction between 8-hydroxyquinoline ruthenium(II) complexes and basic fibroblast growth factors (bFGF): inhibiting angiogenesis and tumor growth through ERK and AKT signaling pathways.
- Source :
-
Metallomics : integrated biometal science [Metallomics] 2014 Mar; Vol. 6 (3), pp. 518-31. Date of Electronic Publication: 2013 Dec 16. - Publication Year :
- 2014
-
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.
- Subjects :
- Angiogenesis Inhibitors chemistry
Angiogenesis Inhibitors therapeutic use
Animals
Antineoplastic Agents chemistry
Antineoplastic Agents therapeutic use
Cell Movement drug effects
Cell Proliferation drug effects
Coordination Complexes chemistry
Coordination Complexes therapeutic use
Hep G2 Cells
Human Umbilical Vein Endothelial Cells
Humans
MAP Kinase Signaling System drug effects
Male
Mice
Mice, SCID
Neoplasms drug therapy
Neoplasms metabolism
Neoplasms pathology
Oxyquinoline chemistry
Oxyquinoline therapeutic use
Proto-Oncogene Proteins c-akt metabolism
Ruthenium chemistry
Signal Transduction drug effects
Angiogenesis Inhibitors pharmacology
Antineoplastic Agents pharmacology
Coordination Complexes pharmacology
Fibroblast Growth Factor 2 metabolism
Oxyquinoline pharmacology
Ruthenium pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1756-591X
- Volume :
- 6
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Metallomics : integrated biometal science
- Publication Type :
- Academic Journal
- Accession number :
- 24336978
- Full Text :
- https://doi.org/10.1039/c3mt00237c