RESUMEN
We report a new osmium(VI) nitrido complex bearing a nonplanar tetradentate ligand with potent anticancer activity. This complex causes mitochondrial damage, which induces liver cancer cell death via oncosis and apoptosis. This is the first osmium-based anticancer candidate that induces oncosis.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Complejos de Coordinación/farmacología , Mitocondrias/efectos de los fármacos , Nitrilos/farmacología , Osmio/farmacología , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Complejos de Coordinación/química , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Mitocondrias/metabolismo , Estructura Molecular , Nitrilos/química , Osmio/químicaRESUMEN
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.
