Cell Death by Polyvinylpyrrolidine-Coated Silver Nanoparticles is Mediated by ROS-Dependent Signaling

Abstract

Silver nanoparticles (AgNPs) are widely used nanoparticles and they are mainly used in antibacterial and personal care products. In this study, we evaluated the effect of AgNPs on cell death induction in the murine dendritic cell line DC2.4. DC2.4 cells exposed to AgNPs showed a marked decrease in cell viability and an induction of lactate dehydrogenase (LDH) leakage in a time- and dose-dependent manner. In addition, AgNPs promoted reactive oxygen species (ROS)-dependent apoptosis and AgNP-induced ROS triggered a decrease in mitochondrial membrane potential. The activation of the intracellular signal transduction pathway was also observed in cells cultured with AgNPs. Taken together, our data demonstrate that AgNPs are able to induce a cytotoxic effect in DCs through ROS generation. This study provides important information about the safety of AgNPs that may help in guiding the development of nanotechnology applications.

Comparative assessment of the apoptotic potential of silver nanoparticles synthesized by Bacillus tequilensis and Calocybe indica in MDA-MB-231 human breast cancer cells: targeting p53 for anticancer therapy

“…Further, polyvinylpyrrolidine-coated AgNPs inhibited cell proliferation and viability, and increased LDH leakage, in a time-and concentration-dependent manner in the murine dendritic DC2.4 cell line (Kang et al). 75 The results from our experiments and the previous literature suggest that AgNPs can reduce the membrane potential of MDA-MB-231 cells. 73 …”

“…ROS target mitochondria and cause DNA damage and apoptosis. 75 Earlier studies have suggested that AgNPs are inducers of ROS in a variety of cells. 10,20,65,76 The exposure of MDA-MB-231 cells to AgNPs could result in the production of ROS, which could explain the outcomes of metabolic and toxicological problems (Figure 8).…”

“…Kang et al reported that AgNPs stimulate ROS-dependent apoptosis and the inhibition of mitochondrial function. 75 Finkel and Holbrook reported that ROS can induce various cellular events, such as cell growth and cell signaling. 77 The production of intracellular ROS has been implicated as a mediator of nanotoxicity, including toxicity of AgNPs in human hepatoma cells.…”

“…88,89 Similarly, several studies reported that polyvinylpyrrolidone (PVP)-coated AgNPs induced p53 in the larval tissue of Drosophila melanogaster. 75,90 Taken together, the induction of the apoptotic pathway is indicated by the phosphorylation of p53 and ERK1/2.…”

“…Similarly, Kang et al did not observe any significant impact of AgNPs on c-Jun in DC2.4 cells. 75 Hsin et al reported that AgNPs activate JNK-dependent mechanisms involved in the mitochondrial pathway of NIH3T3 cells. 79 The Bcl-2 protein family controls mitochondrial outer-membrane permeabilization (MOMP) and can exert their proapoptotic (Bax, Bad, and Bak) or antiapoptotic (Bcl-2 and Bcl-XL) effect by activation or inactivation of an inner mitochondrial permeability transition pore.…”