Cytotoxic activity, DNA damage, cellular uptake, apoptosis and western blot analysis of ruthenium(II) polypyridyl complex against human lung decarcinoma A549 cell

Lai, Shang-Hai; Jiang, Guang-Bin; Jiang, Yao; Li, Wei; Han, Bing-Jie; Zhang, Cheng; Zeng, Chuan-Chuan; Liu, Yun-Jun

doi:10.1016/j.jinorgbio.2015.08.012

Cited by 50 publications

(19 citation statements)

References 41 publications

(39 reference statements)

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“…To generate recombinant viruses, EPC cells were transfected with plasmids pVHSV-D62A and pVHSV-D62A E181A, along with the support plasmids, using a protocol described previously (69). Briefly, plasmid pVHSV or its derivatives were diluted in 500 l of Opti-MEM medium.…”

Section: Methodsmentioning

confidence: 99%

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Role of Viral Hemorrhagic Septicemia Virus Matrix (M) Protein in Suppressing Host Transcription

Qin

Weaver

Pore

et al. 2017

J Virol

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Viral hemorrhagic septicemia virus (VHSV) is a pathogenic fish rhabdovirus found in discrete locales throughout the Northern Hemisphere. VHSV infection of fish cells leads to upregulation of the host's virus detection response, but the virus quickly suppresses interferon (IFN) production and antiviral gene expression. By systematically screening each of the six VHSV structural and nonstructural genes, we identified matrix protein (M) as the virus' most potent antihost protein. Only M of VHSV genotype IV sublineage b (VHSV-IVb) suppressed mitochondrial antiviral signaling protein (MAVS) and type I IFN-induced gene expression in a dose-dependent manner. M also suppressed the constitutively active simian virus 40 (SV40) promoter and globally decreased cellular RNA levels. Chromatin immunoprecipitation (ChIP) studies illustrated that M inhibited RNA polymerase II (RNAP II) recruitment to gene promoters and decreased RNAP II C-terminal domain (CTD) Ser2 phosphorylation during VHSV infection. However, transcription directed by RNAP I to III was suppressed by M. To identify regions of functional importance, M proteins from a variety of VHSV strains were tested in cell-based transcriptional inhibition assays. M of a particular VHSV-Ia strain, F1, was significantly less potent than IVb M at inhibiting SV40/ luciferase (Luc) expression yet differed by just 4 amino acids. Mutation of D62 to alanine alone, or in combination with an E181-to-alanine mutation (D62A E181A), dramatically reduced the ability of IVb M to suppress host transcription. Introducing either M D62A or D62A E181A mutations into VHSV-IVb via reverse genetics resulted in viruses that replicated efficiently but exhibited less cytotoxicity and reduced antitranscriptional activities, implicating M as a primary regulator of cytopathicity and host transcriptional suppression.IMPORTANCE Viruses must suppress host antiviral responses to replicate and spread between hosts. In these studies, we identified the matrix protein of the deadly fish novirhabdovirus VHSV as a critical mediator of host suppression during infection. Our studies indicated that M alone could block cellular gene expression at very low expression levels. We identified several subtle mutations in M that were less potent at suppressing host transcription. When these mutations were engineered back into recombinant viruses, the resulting viruses replicated well but elicited less toxicity in infected cells and activated host innate immune responses more robustly. These data demonstrated that VHSV M plays an important role in mediating both virusinduced cell toxicity and viral replication. Our data suggest that its roles in these two processes can be separated to design effective attenuated viruses for vaccine candidates.

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Section: Methodsmentioning

confidence: 99%

“…Cell lysate was separated by SDS-polyacrylamide gel electrophoresis (PAGE) as previously described (69). Briefly, samples were run on 12.5% gel.…”

Section: Methodsmentioning

confidence: 99%

Role of Viral Hemorrhagic Septicemia Virus Matrix (M) Protein in Suppressing Host Transcription

Qin

Weaver

Pore

et al. 2017

J Virol

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“…Western blot analysis:C ellular protein expression levels were determined by western blot analysis. [40] Protein concentrations were determined by BCA kit (Sigma-Aldrich), and protein bands were detected on X-ray film. b-Actin was used to ensure consistent protein loading in each lane.…”

mentioning

confidence: 99%

Microwave‐Assisted Syntheses of Benzimidazole‐Containing Selenadiazole Derivatives That Induce Cell‐Cycle Arrest and Apoptosis in Human Breast Cancer Cells by Activation of the ROS/AKT Pathway

et al. 2016

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The use of selenium-containing heterocyclic compounds as potent cancer chemopreventive and chemotherapeutic agents has been well documented by a large number of clinical studies. In this study we developed a new approach to synthesize four benzimidazole-containing selenadiazole derivatives (BSeDs). The method uses a combination of peptide coupling reagents and microwave irradiation. This strategy features milder reaction conditions, higher yields, and shorter reaction times. The synthetic BSeDs were identified as potent antiproliferative agents against the human MCF-7 and MDA-MB-231 breast cancer cell lines. Compounds 1 b (5-(6-methyl-1H-benzo[d]imidazol-2-yl)benzo[c][1,2,5]selenadiazole), 1 c (5-(6-chloro-1H-benzo[d]imidazol-2-yl)benzo[c][1,2,5]selenadiazole), and 1 d (5-(6-bromo-1H-benzo[d]imidazol-2-yl)benzo[c][1,2,5]selenadiazole) were found to show greater cytotoxicity against the triple-negative breast cancer cell line MDA-MB-231 than MCF-7, and to exhibit dose-dependent inhibition of cell migration, in which a significant decrease in the zone of cell monolayer wound closure was observed relative to untreated controls. Our results demonstrate that BSeDs can cause cell-cycle arrest and apoptosis in MDA-MB-231 cells by inducing DNA damage, inhibiting protein kinase B (AKT), and activating mitogen-activated protein kinase (MAPK) family members through the overproduction of reactive oxygen species (ROS). Taken together, the results of this study provide a facile microwave-assisted strategy for the synthesis of selenium-containing organic compounds that exhibit a high level of anticancer efficacy.

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“…Complex 1 exhibits a comparable cytotoxicity with complexes 3 and 4 against MG-63 cells, and A549 cells exhibit an almost identical sensitivity to the complexes. By contrast, the cytotoxic activity induced by the complexes is lower than those of cisplatin and other dppz-like ruthenium(II) complexes, particularly, [Ru(dmp) 2 (adppz)](ClO 4 ) 2 (IC 50 ¼ 2.4 ± 0.4 mM against A549) [16] and [Ru(hdpa) 2 (7-F-dppz)](ClO 4 ) 2 (IC 50 ¼ 16 ± 2.5 mM against HeLa) [17], [Ru(phen) 2 (addppn)] 2þ (IC 50 ¼ 6.6 ± 0.6 mM against MG-63) [15] and [Ru(dmp) 2 (pddppn)] 2þ (IC 50 ¼ 1.5 ± 0.3 mM toward A549) [18] under the same conditions. Complex 4 (dmp as ancillary ligand) exhibits the highest cytotoxicity against HepG-2 and HeLa cells, whereas complex 1 (dmb as ancillary ligand) reveals the highest cytotoxic activity toward MG-63 and A549 cells.…”

Section: Cytotoxic Activity In Vitro Studiesmentioning

confidence: 99%

The induction of apoptosis in HepG-2 cells by ruthenium(II) complexes through an intrinsic ROS-mediated mitochondrial dysfunction pathway

Zeng

Lai

Jiang

et al. 2016

European Journal of Medicinal Chemistry

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Cytotoxic activity, DNA damage, cellular uptake, apoptosis and western blot analysis of ruthenium(II) polypyridyl complex against human lung decarcinoma A549 cell

Cited by 50 publications

References 41 publications

Role of Viral Hemorrhagic Septicemia Virus Matrix (M) Protein in Suppressing Host Transcription

Role of Viral Hemorrhagic Septicemia Virus Matrix (M) Protein in Suppressing Host Transcription

Microwave‐Assisted Syntheses of Benzimidazole‐Containing Selenadiazole Derivatives That Induce Cell‐Cycle Arrest and Apoptosis in Human Breast Cancer Cells by Activation of the ROS/AKT Pathway

The induction of apoptosis in HepG-2 cells by ruthenium(II) complexes through an intrinsic ROS-mediated mitochondrial dysfunction pathway

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