Dinuclear ruthenium complexes display loop isomer selectivity to c-MYC DNA G-quadriplex and exhibit anti-tumour activity
| Autor: | Xiuying Qin, Yanhui Zhou, Chuping Zheng, Jie Liu, Ying Liu, Yanan Liu |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Circular dichroism
Stereochemistry Genes myc chemistry.chemical_element Antineoplastic Agents 010402 general chemistry G-quadruplex 01 natural sciences Biochemistry Inorganic Chemistry chemistry.chemical_compound Isomerism Fluorescence Resonance Energy Transfer Humans Protein kinase B biology 010405 organic chemistry Chemistry Circular Dichroism Hep G2 Cells 0104 chemical sciences Ruthenium G-Quadruplexes Förster resonance energy transfer Mitogen-activated protein kinase biology.protein Ruthenium Compounds Selectivity DNA |
| Zdroj: | Journal of Inorganic Biochemistry. 156:122-132 |
| ISSN: | 0162-0134 |
| DOI: | 10.1016/j.jinorgbio.2016.01.001 |
| Popis: | 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}. |
| Databáze: | OpenAIRE |
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