کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1316432 1499431 2016 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Dinuclear ruthenium complexes display loop isomer selectivity to c-MYC DNA G-quadriplex and exhibit anti-tumour activity
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی معدنی
پیش نمایش صفحه اول مقاله
Dinuclear ruthenium complexes display loop isomer selectivity to c-MYC DNA G-quadriplex and exhibit anti-tumour activity
چکیده انگلیسی


• 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}

Dinuclear 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 as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Inorganic Biochemistry - Volume 156, March 2016, Pages 122–132
نویسندگان
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