Silver nanoparticles induce apoptosis and G2/M arrest via PKCζ-dependent signaling in A549 lung cells

Lee, Young Sook; Kim, Dong Ho; Lee, Young Ho; Oh, Jung Hwa; Yoon, Seokjoo; Choi, Mi Sun; Lee, Sung Kyu; Kim, Ji Won; Lee, Kyuhong; Song, Chuyi

doi:10.1007/s00204-011-0714-1

Cited by 119 publications

(68 citation statements)

References 51 publications

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“…Exceptions were clusters 2 and 6, showing an upregulation of anti-apoptotic pathways for Caco-2 cells only. Apoptosis has often been reported to be induced by AgNPs through oxidative stress (Gopinath et al, 2010;Lee et al, 2011) and upregulation of anti-apoptotic pathways could be the result of an adaptation mechanism responding to stress, as previously reported in HepG2 cells exposed to AgNPs (Brzoska et al, 2015). As the Caco-2 cells in the present study appeared to have higher stress levels than the MCF-7 cells, possibly in these cells adaptation processes were activated.…”

Section: Mechanistic Responses In Caco-2 and Mcf-7 Cellssupporting

confidence: 82%

Different responses of Caco-2 and MCF-7 cells to silver nanoparticles are based on highly similar mechanisms of action

et al. 2016

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The mode of action of silver nanoparticles (AgNPs) is suggested to be exerted through both Ag + and AgNP dependent mechanisms. Ingestion is one of the major NP exposure routes, and potential effects are often studied using Caco-2 cells, a well-established model for the gut epithelium. MCF-7 cells are epithelial breast cancer cells with extensive well-characterized toxicogenomics profiles. In the present study, we aimed to gain a deeper understanding of the cellular molecular responses in Caco-2 and MCF-7 cells after AgNP exposure in order to evaluate whether epithelial cells derived from different tissues demonstrated similar responses. These insights could possibly reduce the size of cell panels for NP hazard identification screening purposes. AgNPs of 20, 30, 60, and 110 nm, and AgNO 3 were exposed for 6 h and 24 h. AgNPs were shown to be taken up and dissolve intracellularly. Compared with MCF-7 cells, Caco-2 cells showed a higher sensitivity to AgNPs, slower gene expression kinetics and absence of NP size-dependent responses. However, on a molecular level, no significant differences were observed between the two cell types. Transcriptomic analysis showed that Ag(NP) exposure caused (oxidative) stress responses, possibly leading to cell death in both cell lines. There was no indication for effects specifically induced by AgNPs. Responses to AgNPs appeared to be induced by silver ions released from the AgNPs. In conclusion, differences in mRNA responses to AgNPs between Caco-2 and MCF-7 cells were mainly related to timing and magnitude, but not to a different underlying mechanism.

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Section: Mechanistic Responses In Caco-2 and Mcf-7 Cellssupporting

confidence: 82%

Different responses of Caco-2 and MCF-7 cells to silver nanoparticles are based on highly similar mechanisms of action

et al. 2016

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“…61 Lee et al 62 observed that the LDH level increased 210% when cells were cultivated for 48 hours in a culture medium containing AgNPs at 100 µg/mL, and found that AgNPs could induce the release of LDH in a concentrationand time-dependent manner, indicating that AgNPs reduced the membrane potential in A549 cells. We found that an IC 50 concentration of 6.0 µg/mL was significant to inhibit cell growth and sufficient to induce cell death.…”

mentioning

confidence: 99%

Green synthesis of silver nanoparticles using Ganoderma neo-japonicum Imazeki: a potential cytotoxic agent against breast cancer cells

Gurunathan¹,

Raman²,

Malek³

et al. 2013

IJN

132

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Background Silver nanoparticles (AgNPs) are an important class of nanomaterial for a wide range of industrial and biomedical applications. AgNPs have been used as antimicrobial and disinfectant agents due their detrimental effect on target cells. The aim of our study was to determine the cytotoxic effects of biologically synthesized AgNPs using hot aqueous extracts of the mycelia of Ganoderma neo-japonicum Imazeki on MDA-MB-231 human breast cancer cells. Methods We developed a green method for the synthesis of water-soluble AgNPs by treating silver ions with hot aqueous extract of the mycelia of G. neo-japonicum. The formation of AgNPs was characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction, dynamic light scattering, and transmission electron microscopy. Furthermore, the toxicity of synthesized AgNPs was evaluated using a series of assays: such as cell viability, lactate dehydrogenase leakage, reactive oxygen species generation, caspase 3, DNA laddering, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling in human breast cancer cells (MDA-MB-231). Results The ultraviolet-visible absorption spectroscopy results showed a strong resonance centered on the surface of AgNPs at 420 nm. The X-ray diffraction analysis confirmed that the synthesized AgNPs were single-crystalline, corresponding with the result of transmission electron microscopy. Treatment of MDA-MB-231 breast cancer cells with various concentrations of AgNPs (1–10 μg/mL) for 24 hours revealed that AgNPs could inhibit cell viability and induce membrane leakage in a dose-dependent manner. Cells exposed to AgNPs showed increased reactive oxygen species and hydroxyl radical production. Furthermore, the apoptotic effects of AgNPs were confirmed by activation of caspase 3 and DNA nuclear fragmentation. Conclusion The results indicate that AgNPs possess cytotoxic effects with apoptotic features and suggest that the reactive oxygen species generated by AgNPs have a significant role in apoptosis. The present findings suggest that AgNPs could contribute to the development of a suitable anticancer drug, which may lead to the development of a novel nanomedicine for the treatment of cancers.

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“…Such proposed mechanisms include complexing with thiol [1], sulfydryl, amino, or hydroxyl functional groups [13], competing with copper ions as a cofactor in transport or enzymatic reactions [13], general toxicity [13] [22], disruption of aliphatic carbon-hydrogen bonds by insertion of carbenes [23], DNA damage by arene-purine hydrophobic interactions [23], direct binding to DNA [1], increased permeability and disruption of cell membranes [1], and inhibition of respiratory [1] or signaling [21] enzymes.…”

Section: Introductionmentioning

confidence: 99%

Broad-Spectrum Antibacterial Characteristics of Four Novel Borate-Based Bioactive Glasses

Ottomeyer¹,

Mohammadkah²,

Day³

et al. 2016

AiM

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Bioactive glasses have been developed for medical applications in the body for bone and tissue repair and regeneration. We have developed a borate-containing bioactive glass (13-93B3, referred to as B3), which is undergoing clinical trials to assess its wound-healing properties. To complement the healing properties of B3, metal ion dopants have been added to enhance its antimicrobial properties. Bioactive glasses doped with silver, gallium or iodine ions were found to have broad spectrum antimicrobial effects on clinically relevant bacteria including MRSA. While the B3 glass alone was sufficient to produce antibacterial effects on select bacteria, adding dopants enhanced the broad-spectrum antibacterial properties: Live-Dead staining fluorescence microscopy suggests cell membrane integrity is disrupted in gram positive bacteria exposed to the glass compounds, but not gram negative bacteria, indicating multiple mechanisms of action for each glass formulation.

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Silver nanoparticles induce apoptosis and G2/M arrest via PKCζ-dependent signaling in A549 lung cells

Cited by 119 publications

References 51 publications

Different responses of Caco-2 and MCF-7 cells to silver nanoparticles are based on highly similar mechanisms of action

Different responses of Caco-2 and MCF-7 cells to silver nanoparticles are based on highly similar mechanisms of action

Green synthesis of silver nanoparticles using Ganoderma neo-japonicum Imazeki: a potential cytotoxic agent against breast cancer cells

Broad-Spectrum Antibacterial Characteristics of Four Novel Borate-Based Bioactive Glasses

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