Article ID Journal Published Year Pages File Type
1316432 Journal of Inorganic Biochemistry 2016 11 Pages PDF
Abstract

•The two ruthenium complexes are dinuclear ruthenium complexes.•The two ruthenium complexes display loop isomer selectivity to c-MYC G-quadruplex DNA.•The dinuclear complex with phenanthroline ligand has a greater effect on the 1:2:1 and 2:1:1 loop isomers.•The two dinuclear Ru(II) complexes can reduce the expression of c-MYC gene expression.•The dinuclear Ru(II) complexes can induce apoptosis in HepG2 cells.

G-quadruplex DNA, especially the cellular-myelocytomatosis viral oncogene (c-MYC) is closely associated with cell-cycle regulation, proliferation of tumour cells. In this work, the interaction between the c-MYC and two dinuclear Ru(II) complexes [(bpy)2Ru(bpibp)Ru(bpy)2](ClO4)4 (compound 1) and [(phen)2Ru(bpibp)Ru(phen)2](ClO4)4 (compound 2) have been studied. The data from UV–Visible, PCR-stop and Fluorescence resonance energy transfer (FRET) showed that two complexes can stabilize the structure of G-quadruplex in the c-MYC promoter and targeting the G-quadruplex loop isomers. Interestingly, the complex 2 has a greater effect on the 1:2:1 and 2:1:1 loop isomers while the 1 prefers to the 1:2:1 isomers. The mechanism studies revealed that complexes can induce apoptosis in HepG2 cells by generating ROS metabolites, triggering mitochondrial membrane potential loss and down-regulation of P-Akt (Akt also known as protein kinase B), P-p44/42 MAP kinase protein (P-p44/42), and c-MYC. Taken together, these results suggested that the two dinuclear complexes may both be candidates as anti-tumour agents as they may reduce the c-MYC gene expression. {bpibp: 4, 4′-bis (1, 10-phenanthroline-[5, 6-d] imidazole-2-yl)-biphenyl, bpy: 2,2-bipyridine, phen: 1,10-phenanthroline}

Graphical abstractDinuclear ruthenium (II) complexes can induce the depletion of mitochondrial membrane potential (MMP) and suppress the Akt (Protein Kinase B) and p-44/42 signalling pathways and inhibited cellular proliferation.Figure optionsDownload full-size imageDownload as PowerPoint slide

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Physical Sciences and Engineering Chemistry Inorganic Chemistry
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