Ruthenium(II) complexes: DNA-binding, cytotoxicity, apoptosis, cellular localization, cell cycle arrest, reactive oxygen species, mitochondrial membrane potential and western blot analysis

• Four new Ru(II) complexes 1, 2, 3 and 4 were synthesized and characterized.
• The DNA-binding behaviors were studied.
• The cytotoxicity of these complexes was evaluated by MTT method.
• The apoptosis, cellular uptake and cell cycle arrest were investigated.
• ROS, mitochondrial membrane potential and western blot analysis were assayed.

The aim of our study was to investigate DNA-binding and cytotoxic activity of the four new Ru(II) polypyridyl complexes [Ru(dmb)2(HMHPIP)](ClO4)2 (1), [Ru(bpy)2(HMHPIP)](ClO4)2 (2), [Ru(phen)2(HMHPIP)](ClO4)2 (3) and [Ru(dmp)2(HMHPIP)](ClO4)2 (4). The complexes interact with DNA through intercalative mode and show relatively high cytotoxic activity against A549 cells, no cytotoxicity toward MG-63 cells. Complexes 1–4 can enhance the levels of ROS in A549 cells and induce the decrease of the mitochondrial membrane potential. These complexes inhibit the cell growth in A549 cells at G0/G1 or S phase. Complex 3 activated caspase 7, and down-regulated the expression of the anti-apoptotic protein Bcl-2. Complexes 1–4 induce apoptosis in A549 cells through ROS-mediated mitochondrial dysfunction pathway.

Complexes 1–4 were synthesized and characterized. The cytotoxicity was assessed by MTT method. The apoptosis, cellular uptake, cell cycle arrest, ROS, mitochondrial membrane potential, western blot analysis and DNA-binding were studied.Figure optionsDownload as PowerPoint slide