Ruthenium complexes with phenylterpyridine derivatives target cell membrane and trigger death receptors-mediated apoptosis in cancer cells

Deng, Zhiqin; Gao, Pan; Yu, Liu; Ma, Bin; You, Yi; Chan, Leung; Mei, Chaoming; Chen, Tianfeng

doi:10.1016/j.biomaterials.2017.03.017

Cited by 63 publications

(38 citation statements)

References 66 publications

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“…199–204 Moreover, the Chen group found that 12f triggered cell apoptosis via the extrinsic pathway by inducing the activation of caspase-9. 205 This complex firstly accumulated on cell membranes by a transferrin receptor-mediated endocytosis, promoting access to the cell cytoplasm and ultimately, the nucleus. Notably, the complex possessed more prolonged circulation time in the blood, comparable antitumor efficacy and significant lower toxicity in vivo experiments in mice, compared to cisplatin.…”

Section: Ruthenium(ii) Polypyridyl Complexesmentioning

confidence: 99%

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

et al. 2017

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Cancer is rapidly becoming the top killer in the world. Most of the FDA approved anticancer drugs are organic molecules, while metallodrugs are very scarce. The advent of first metal based therapeutic agent, cisplatin, launched a new era in the application of transition metal complexes for therapeutic design. Due to their unique and versatile biochemical properties, ruthenium-based compounds have emerged as promising anti-cancer agents that serve as alternatives to cisplatin and its derivertives. The ruthenium(III) complexes have successfully been used in clinical research and their mechanisms of anticancer action have been reported in large volumes over the past few decades. Ruthenium(II) complexes have also attracted significant attention as anticancer candidates; however, only few of them have been reported comprehensively. In this review, we discuss the development of ruthenium(II) complexes as anticancer candidates and biocatalysts, including arene ruthenium complexes, polypyridyl ruthenium complexes, and ruthenium nanomaterial complexes. This review focuses on the likely mechanisms of action of ruthenium(II)-based anticancer drugs and the relationship between their chemical structures and biological properties. This review also highlights the catalytic activity and the photoinduced activation of ruthenium(II) complexes, their targeted delivery, and their activity in nanomaterial systems.

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Section: Ruthenium(ii) Polypyridyl Complexesmentioning

confidence: 99%

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

et al. 2017

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“…The anticancer potential of ruthenium complexes is associated with targets and signaling pathways and depends on the properties of the complex, the ligands, and the sites of tumors (14). For example, ruthenium complexes induced cell death might involve the mitochondria-mediated signaling pathway, the death receptor-mediated signaling pathway, and the endoplasmic reticulum signaling pathways (15)(16)(17)(18). Accordingly, the various targets of ruthenium complexes for cell death are mitochondria, endoplasmic reticulum, and multiple molecules (19)(20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Combination of Ruthenium Complex and Doxorubicin Synergistically Inhibits Cancer Cell Growth by Down-Regulating PI3K/AKT Signaling Pathway

et al. 2020

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Combinational use of drugs has been a common strategy in cancer treatment because of synergistic advantages in reducing dose and toxicity, minimizing or delaying drug resistance. To improve the efficacy of chemotherapy, various potential combinations have been investigated. Ruthenium complex is considered a potential alternative of the platinum-based drugs due to its significant efficacy and safety. Previously, we reported that ruthenium(II) complex ( -Ru1) has great anticancer potential and minor toxicity toward normal tissues. However, the therapeutic efficacy and mechanism of action of ruthenium(II) complex combined with other anticancer drugs is still unknown. Here, we investigated the combinational effect of -Ru1 and doxorubicin in different cancer cells. The data assessed by Chou-Talalay method showed significant synergism in MCF-7 cells. Furthermore, the results in antiproliferation efficacy indicated that the combination showed strong cytotoxicity and increasing apoptosis of MCF-7 cells in 2D and 3D multicellular tumor spheroids (MCTSs). Significant inhibition of MCF-7 cells accompanied with increased ROS generation was observed. Furthermore, the expression of PI3K/AKT was significantly down-regulated, while the expression of PTEN was strongly up-regulated in cells treated with combination of -Ru1 and doxorubicin. The expression of NF-κB and XIAP decreased while the expression of P53 increased and associated with apoptosis. These findings suggest that the combination of ruthenium complex and doxorubicin has a significant synergistic effect by down-regulating the PI3K/AKT signaling pathway in MCF-7 cells. This study may trigger more research in ruthenium complex and combination therapy that will be able to provide opportunities for developing better therapeutics for cancer treatment.

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“…[11][12][13][14] Furthermore, comparedt op latinum and ruthenium complexes,copper complexes have demonstratedgood antitumor activity with fewer side effects. [20][21][22][23][24] In as imilar fashion, metal complexes with Schiff-base scaffolds have been effectively applied as antibacterial chemotherapeutic moieties in medicine. [20][21][22][23][24] In as imilar fashion, metal complexes with Schiff-base scaffolds have been effectively applied as antibacterial chemotherapeutic moieties in medicine.…”

Section: Introductionmentioning

confidence: 99%

“…[15][16][17][18][19] Moreover,av ariety of pyridine-ligand-based complexes have exhibited high reactivity toward DNA cleavage and cell apoptosis. [20][21][22][23][24] In as imilar fashion, metal complexes with Schiff-base scaffolds have been effectively applied as antibacterial chemotherapeutic moieties in medicine. [25,26] The chemotherapeutic effect of Cu II -containing Schiff-base complexes may be enhanced by tuningt he electronic properties of the metal centero rt he ligandst hrough coordination.…”

Section: Introductionmentioning

confidence: 99%

Photocytotoxic Copper(II) Complexes with Schiff‐Base Scaffolds for Photodynamic Therapy

Lin

Chiu

Hsu

et al. 2018

Chemistry A European J

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Photodynamic therapy (PDT) is a promising and minimally invasive method for the treatment of superficial diseases, and photosensitizers with high phototoxicity indices (defined as (IC )/(IC )) are essential for the development of ideal photosensitizing properties for this technology. Herein, we report a series of photocytotoxic copper(II) complexes [Cu( QYMP)(dppn)] ( QYMP=N,N,O-tridentate Schiff-base derivatives, dppn=benzo[i]dipyrido[3,2-a;2',3'-c]phenazine), the structures of which have been confirmed by mass spectrometry and FTIR spectroscopy. X-ray crystallography revealed that the CuN O core of the [Cu( QYMP)(dppn)](ClO ) complex (3) has a distorted square-pyramidal geometry. Phototoxicity indices of 329 against human squamous cell carcinoma (SCC15) and 296 against basal cell carcinoma (BCC) cell lines have been determined with [Cu( QYMP)(dppn)](ClO ) (4). This can be attributed to the formation of reactive oxygen species, cell apoptosis, and caspase-3 activation, indicating high potential of complex 4 as a photosensitizer candidate in PDT. Thus, copper complexes bearing suitable Schiff-base ligands with a dppn co-ligand may be considered for the design of efficient metal-based anticancer agents for PDT.

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Ruthenium complexes with phenylterpyridine derivatives target cell membrane and trigger death receptors-mediated apoptosis in cancer cells

Cited by 63 publications

References 66 publications

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

Combination of Ruthenium Complex and Doxorubicin Synergistically Inhibits Cancer Cell Growth by Down-Regulating PI3K/AKT Signaling Pathway

Photocytotoxic Copper(II) Complexes with Schiff‐Base Scaffolds for Photodynamic Therapy

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