5-Bromo-oxoisoaporphine platinum(II) complexes exhibit tumor cell cytotoxcicity via inhibition of telomerase activity and disruption of c-myc G-quadruplex DNA and mitochondrial functions

Wei, Zu‐Zhuang; Qin, Qi‐Pin; Meng, Ting; Deng, Cai-Xing; Liang, Hong; Chen, Zhen-Feng

doi:10.1016/j.ejmech.2017.12.092

Cited by 31 publications

(16 citation statements)

References 73 publications

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“…[36] Figure 10). [43] According to the results, the two new complexes were more selective for Hep-G2c ells than that of normal cells (HL-7702,W I-38, and L-o2 cell lines). Compound 33 showed the best inhibitory capacity against Hep-G2, with IC50 values up to 5.06 mm, whereas 32 reached 10.12 mm.F urther persuasive pharmacological research was also performed to determinet heir mechanism of cell apoptosis.…”

Section: Metal and Oxoisoaporphinec Omplexesmentioning

confidence: 92%

Oxoisoaporphine Alkaloids: Prospective Anti‐Alzheimer's Disease, Anticancer, and Antidepressant Agents

2018

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Oxoisoaporphine alkaloids are a family of oxoisoquinoline-derived alkaloids that were first isolated from the rhizome of Menispermum dauricum DC. (Menispermaceae). It has been demonstrated that oxoisoaporphine alkaloids possess various biological properties, such as cholinesterase and β-amyloid inhibition, acting as a topoisomerase intercalator, monoamine oxidase A inhibition, and are expected to become anti-Alzheimer's disease, anticancer, and antidepressant drugs. This review provides an overview of natural sources, synthetic routes, bioactivities, structure-function relationship, and modification investigations into oxoisoaporphine alkaloids, with the aim of providing references to the structure-activity relationships for the design and development of oxoisoaporphine derivatives with higher efficacy and therapeutic potential.

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Section: Metal and Oxoisoaporphinec Omplexesmentioning

confidence: 92%

Oxoisoaporphine Alkaloids: Prospective Anti‐Alzheimer's Disease, Anticancer, and Antidepressant Agents

2018

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“…For instance, EGCG significantly affected the expression of bax, bad, bcl-2, and bcl-xl, members from the Bcl-2 family, which are key players in apoptosis. 26 EGCG upregulated the expression of pro-apoptotic genes, like bad, bax, smac, 27 apaf, 28 puma, 29 and pten; and, on the other hand, EGCG inhibited the expression of anti-apoptosis genes bcl-2, bcl-xl, survivin, 30 and c-myc. 31 The modulation of these key apoptotic players provides insight into the mechanism by which EGCG induces apoptosis.…”

Section: Papermentioning

confidence: 99%

Suppressing glucose metabolism with epigallocatechin-3-gallate (EGCG) reduces breast cancer cell growth in preclinical models

et al. 2018

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“…This leads to telomere uncapping, cell cycle arrest, or apoptosis [ 20 , 21 , 22 , 23 ]. Metallic complexes are particularly suitable as G4-ligands [ 24 , 25 ] that can disturb telomere functions [ 26 , 27 , 28 , 29 , 30 , 31 ]. Among them, some Pt II complexes bearing a labile halogen ligand (Cl − or I − ) are capable of interacting with the G4 by direct coordination to the nucleobase (adenines or guanines) and trap them irreversibly [ 29 , 32 , 33 , 34 , 35 , 36 ] after stacking to the structure [ 37 ].…”

Section: Introductionmentioning

confidence: 99%

Platinum Complexes Can Bind to Telomeres by Coordination

Saker

Ali

Masserot

et al. 2018

IJMS

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It is suggested that several compounds, including G-quadruplex ligands, can target telomeres, inducing their uncapping and, ultimately, cell death. However, it has never been demonstrated whether such ligands can bind directly and quantitatively to telomeres. Here, we employed the property of platinum and platinum-G-quadruplex complexes to target G-rich sequences to investigate and quantify their covalent binding to telomeres. Using inductively coupled plasma mass spectrometry, surprisingly, we found that, in cellulo, in the presence of cisplatin, a di-functional platinum complex, telomeric DNA was platinated 13-times less than genomic DNA in cellulo, as compared to in vitro data. On the contrary, the amount of mono-functional platinum complexes (Pt-ttpy and Pt-tpy) bound either to telomeric or to genomic DNA was similar and occurred in a G-quadruplex independent-manner. Importantly, the quantification revealed that the low level of cisplatin bound to telomeric DNA could not be the direct physical cause of TRF2 displacement from telomeres. Altogether, our data suggest that platinum complexes can affect telomeres both directly and indirectly.

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5-Bromo-oxoisoaporphine platinum(II) complexes exhibit tumor cell cytotoxcicity via inhibition of telomerase activity and disruption of c-myc G-quadruplex DNA and mitochondrial functions

Cited by 31 publications

References 73 publications

Oxoisoaporphine Alkaloids: Prospective Anti‐Alzheimer's Disease, Anticancer, and Antidepressant Agents

Oxoisoaporphine Alkaloids: Prospective Anti‐Alzheimer's Disease, Anticancer, and Antidepressant Agents

Suppressing glucose metabolism with epigallocatechin-3-gallate (EGCG) reduces breast cancer cell growth in preclinical models

Platinum Complexes Can Bind to Telomeres by Coordination

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