Journal
JOURNAL OF INORGANIC BIOCHEMISTRY
Volume 156, Issue -, Pages 122-132Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2016.01.001
Keywords
Dinuclear ruthenium complexes; c-MYC DNA; Cell apoptosis
Funding
- National Natural Science Foundation of China [21171070, 21371075]
- Natural Science Foundation of Guangdong Province [2014A030311025]
- China Postdoctoral Science Foundation
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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)(2)Ru(bpibp)Ru(bpy)(2)) (ClO4)(4) (compound 1) and [(Phen)(2)Ru(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}(C) 2016 Published by Elsevier Inc.
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