Abstract
The osmium(vi) nitrido complex [OsVI(N)(sap)(py)Cl] is a potential anti-cancer drug with promising in vitro antiproliferative activities toward a panel of cancer cell lines, including cisplatin-resistant cells (IC50 values of 2.8-13.8 μM). This drug targets DNA and changes its conformation via covalent binding and insertion. In vitro studies indicate that the drug induces HepG2 cells G2/M phase arrest, disrupts the mitochondrial membrane potential and causes caspase-mediated apoptosis. Further in vivo studies using HepG2-bearing nude mice reveal that this drug not only shows good antitumor efficacy of inhibiting tumor growth, but also does not show the side effect of weight loss.
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects*
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Caspases / metabolism*
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Coordination Complexes / chemical synthesis
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Coordination Complexes / chemistry
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Coordination Complexes / pharmacology*
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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Hep G2 Cells
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Humans
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Liver Neoplasms, Experimental / drug therapy
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Liver Neoplasms, Experimental / metabolism
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Liver Neoplasms, Experimental / pathology
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Membrane Potential, Mitochondrial / drug effects
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Mice
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Mice, Nude
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Models, Molecular
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Molecular Structure
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Nitriles / chemistry
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Nitriles / pharmacology
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Osmium / chemistry
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Osmium / pharmacology
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Structure-Activity Relationship
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Coordination Complexes
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Nitriles
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Osmium
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Caspases