A cytotoxic nitrido-osmium(VI) complex induces caspase-mediated apoptosis in HepG2 cancer cells

Dalton Trans. 2020 Dec 15;49(47):17173-17182. doi: 10.1039/d0dt02715d.

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

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Caspases / metabolism*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms, Experimental / drug therapy
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Nude
  • Models, Molecular
  • Molecular Structure
  • Nitriles / chemistry
  • Nitriles / pharmacology
  • Osmium / chemistry
  • Osmium / pharmacology
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Nitriles
  • Osmium
  • Caspases