Ruthenium(II) complexes as apoptosis inducers by stabilizing c-myc G-quadruplex DNA

Zhang, Zhao; Wu, Qiong; Wu, Xiaohui; Sun, Fenyong; Chen, Lanmei; Chen, Jin-Chan; Yang, Suzhen; Mei, Wenjie

doi:10.1016/j.ejmech.2014.04.070

Cited by 51 publications

(24 citation statements)

References 32 publications

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“…For 1-3, the typical signals of 2,2′-bipyridine, 4,4′-dimethyl-2,2′-bipyridine, and 1,10-phenanthroline were assigned between 7 and 9 ppm with some differences, which is in agreement with similar arene ruthenium complexes with quinolones [25]. The clear characterization of the complexes' structures facilitates the understanding of their anticancer mechanisms [26].…”

Section: Dna-binding Propertiesmentioning

confidence: 94%

Synthesis, characterization and DNA-binding properties of Ru(II) complexes coordinated by ofloxacin as potential antitumor agents

Wang

Zeng

et al. 2015

Journal of Coordination Chemistry

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Three Ru complexes coordinated by oxfloxacin, [Ru(L) 2 (OFX)]Cl·2H 2 O (L = bpy, 1; dmbpy, 2; phen, 3; and OFX = ofloxacin), were synthesized and characterized. These complexes can inhibit the growth of cervical cancer HeLa cells efficiently. Furthermore, these three complexes exhibited excellent binding affinities with DNA, as confirmed by spectroscopy methods and viscosity experiments. Therefore, the synthesized Ru(II) complexes have excellent DNA-binding abilities with potential applications in cancer chemotherapy.

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Section: Dna-binding Propertiesmentioning

confidence: 94%

Synthesis, characterization and DNA-binding properties of Ru(II) complexes coordinated by ofloxacin as potential antitumor agents

Wang

Zeng

et al. 2015

Journal of Coordination Chemistry

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“…organoruthenium(II) anticancer complexes and also indicate that G-quadruplex DNA might be a potential target of organoruthenium(II) anticancer complexes. [16][17][18] The 3′-ends of the human chromosome are overhanging single-stranded forms consisting of tandem repeats of the sequence d(TTAGGG). 19,20 The G-rich telomeric sequence can fold into a G-quadruplex through a network of Hoogsteen hydrogen bonds between G bases stabilized by monovalent cations.…”

Section: N7 Of Guanine (G)mentioning

confidence: 99%

“…Interestingly, despite the fact that the T‐bound ruthenated single‐stranded DNA was not thermodynamically stable, the T bases in the human telomeric G‐quadruplex DNA were found to be both kinetically and thermodynamically competitive with G bases for binding to ruthenium complexes . These results suggest that thymine bases may play a unique role in the pathways of ruthenation of DNA by organoruthenium(II) anticancer complexes and also indicate that G‐quadruplex DNA might be a potential target of organoruthenium(II) anticancer complexes …”

Section: Introductionmentioning

confidence: 97%

Selective binding of an organoruthenium complex to G‐rich human telomeric sequence by tandem mass spectrometry

Cheng

Zeng

Cheng

et al. 2018

Rapid Comm Mass Spectrometry

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Rationale Human telomeric DNA is reported to be a potential target for anticancer organometallic ruthenium(II) complexes, however, the interaction sites were not clearly discriminated and identified. Methods In the current study, tandem mass spectrometry (MS/MS) using collision‐induced dissociation (CID) was firstly introduced to identify the interaction sites of an organometallic ruthenium(II) complex [(η6‐biphenyl)Ru(en)Cl][PF6] (1; en = ethylenediamine) with 5′‐T1T2A3G4G5G6‐3′ (I), the repeating unit of human telomeric DNA, in both positive‐ and negative‐ion mode at a low reaction molar ratio (1/I = 0.2) which was applied to preserve the site selectivity. Results Mass spectrometric results showed that mono‐ruthenated I was the main product under the conditions. In positive‐ion mode, MS/MS results indicated that ruthenium complex 1 binds to T2 or G6 in strand I. However, in negative‐ion mode, no efficient information was obtained for exact identification of ruthenation sites which may be attributed to losses of fragment ions due to charge neutralization by the coordination of the positively charged ruthenium complex to the short MS/MS fragments. Conclusions This is the first report of using top‐down MS to characterize the interactions of organometallic ruthenium(II) complexes and human telomeric DNA. Thymine can be thermodynamically competitive with guanine for binding to ruthenium complexes even at low reaction molar ratio, which inspired us to explore in greater depth the significance of thymine binding.

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“…By contrast, evidence has previously showed that the guanine-rich sequence of the c-myc promoter forms G-quadruplex structures because of three or four guanine bases that are associated in a cyclic array via Hoogsteen hydrogen bonding arrangements3233. Studies in our laboratory showed that ruthenium (II) complexes can also facilitate stability of the c-myc G-quadruplex DNA3435.…”

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confidence: 78%

Self-assembly of c-myc DNA promoted by a single enantiomer ruthenium complex as a potential nuclear targeting gene carrier

Mei

Zheng

et al. 2016

Sci Rep

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Gene therapy has long been limited in the clinic, due in part to the lack of safety and efficacy of the gene carrier. Herein, a single enantiomer ruthenium(II) complex, Λ-[Ru(bpy)2(p-BEPIP)](ClO4)2 (Λ-RM0627, bpy = 4,4′-bipyridine, p-BEPIP = 2-(4-phenylacetylenephenyl)imidazole [4,5f][1, 10] phenanthroline), has been synthesized and investigated as a potential gene carrier that targets the nucleus. In this report, it is shown that Λ-RM0627 promotes self-assembly of c-myc DNA to form a nanowire structure. Further studies showed that the nano-assembly of c-myc DNA that induced Λ-RM0627 could be efficiently taken up and enriched in the nuclei of HepG2 cells. After treatment of the nano-assembly of c-myc DNA with Λ-RM0627, over-expression of c-myc in HepG2 cells was observed. In summary, Λ-RM0627 played a key role in the transfer and release of c-myc into cells, which strongly indicates Λ-RM0627 as a potent carrier of c-myc DNA that targets the nucleus of tumor cells.

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Ruthenium(II) complexes as apoptosis inducers by stabilizing c-myc G-quadruplex DNA

Cited by 51 publications

References 32 publications

Synthesis, characterization and DNA-binding properties of Ru(II) complexes coordinated by ofloxacin as potential antitumor agents

Synthesis, characterization and DNA-binding properties of Ru(II) complexes coordinated by ofloxacin as potential antitumor agents

Selective binding of an organoruthenium complex to G‐rich human telomeric sequence by tandem mass spectrometry

Self-assembly of c-myc DNA promoted by a single enantiomer ruthenium complex as a potential nuclear targeting gene carrier

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