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J Biol Inorg Chem. 2013 Dec;18(8):873-82. doi: 10.1007/s00775-013-1032-2. Epub 2013 Aug 30.

Cytotoxicity, apoptosis, cell cycle arrest, reactive oxygen species, mitochondrial membrane potential, and Western blotting analysis of ruthenium(II) complexes.

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1
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China.

Abstract

Three new ruthenium(II) complexes-[Ru(bpy)2(adppz)](ClO4)2, [Ru(dmb)2(adppz)](ClO4)2, and [Ru(dmp)2(adppz)](ClO4)2 (bpy is 2,2'-bipyridine, adppz is 7-aminodipyrido[3,2-a:2',3'-c]phenazine, dmb is 4,4'-dimethyl-2,2'-bipyridine, and dmp is 2,9-dimethyl-1,10-phenanthroline)-were synthesized. [Ru(dmp)2(adppz)](ClO4)2 exhibits higher cytotoxicity than cisplatin toward A549, MG-63, and SKBR-3 cells. The apoptosis and cellular uptake were studied by fluorescence microscopy. [Ru(dmp)2(adppz)](ClO4)2 enhances the level of reactive oxygen species (ROS) and decreases the mitochondrial membrane potential. These complexes induce cell cycle arrest in S phase in BEL-7402 cells, and inhibit the antiproliferation of SKBR-3 cells at G0/G1 phase. Western blotting analysis shows that [Ru(dmp)2(adppz)](ClO4)2 induces apoptosis in BEL-7402 cells through activation of caspaseĀ 3, caspaseĀ 7, and procaspase 7 and ROS-mediated mitochondrial dysfunction pathways.

PMID:
23989405
DOI:
10.1007/s00775-013-1032-2
[Indexed for MEDLINE]

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