Anticancer Activity Studies of Ruthenium(II) Complex Toward Human Osteosarcoma HOS Cells

J Membr Biol. 2016 Aug;249(4):483-92. doi: 10.1007/s00232-016-9889-y. Epub 2016 Mar 23.

Abstract

A new Ru(II) complex [Ru(dmp)2(NMIP)](ClO4)2 (dmp = 2,9-dimethyl-1,10-phenanthroline, NMIP = 2'-(2″-nitro-3″,4″-methylenedioxyphenyl)imidazo[4',5'-f][1,10]-phenanthroline) was synthesized and characterized by elemental analysis, ESI-MS and (1)H NMR. The cytotoxic activity of the complex against MG-63, U2OS, HOS, and MC3T3-e1 cell lines was investigated by MTT method. The complex shows moderate cytotoxicity toward HOS (IC50 = 35.6 ± 2.6 µM) and MC3T3-e1 (IC50 = 41.6 ± 2.8 µM) cell lines. The morphological studies show that the complex can induce apoptosis in HOS cells and cause an increase of reactive oxygen species levels and a decrease in the mitochondrial membrane potential. The cell cycle distribution demonstrates that the complex inhibits the cell growth at S phase. Additionally, the antitumor activity in vivo reveals that the complex can induce a decrease in tumor weight.

Keywords: Apoptosis; Cell cycle arrest; Cytotoxicity in vitro and in vivo; Reactive oxygen species; Ruthenium(II) complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Molecular Structure
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Osteosarcoma / drug therapy
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • Reactive Oxygen Species / metabolism
  • Ruthenium* / chemistry
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Organometallic Compounds
  • Reactive Oxygen Species
  • Ruthenium