Cerium Oxide Nanoparticles Induced Toxicity in Human Lung Cells: Role of ROS Mediated DNA Damage and Apoptosis

Abstract

Cerium oxide nanoparticles (CeO2 NPs) have promising industrial and biomedical applications. In spite of their applications, the toxicity of these NPs in biological/physiological environment is a major concern. Present study aimed to understand the molecular mechanism underlying the toxicity of CeO2 NPs on lung adenocarcinoma (A549) cells. After internalization, CeO2 NPs caused significant cytotoxicity and morphological changes in A549 cells. Further, the cell death was found to be apoptotic as shown by loss in mitochondrial membrane potential and increase in annexin-V positive cells and confirmed by immunoblot analysis of BAX, BCl-2, Cyt C, AIF, caspase-3, and caspase-9. A significant increase in oxidative DNA damage was found which was confirmed by phosphorylation of p53 gene and presence of cleaved poly ADP ribose polymerase (PARP). This damage could be attributed to increased production of reactive oxygen species (ROS) with concomitant decrease in antioxidant “glutathione (GSH)” level. DNA damage and cell death were attenuated by the application of ROS and apoptosis inhibitors N-acetyl-L- cysteine (NAC) and Z-DEVD-fmk, respectively. Our study concludes that ROS mediated DNA damage and cell cycle arrest play a major role in CeO2 NPs induced apoptotic cell death in A549 cells. Apart from beneficial applications, these NPs also impart potential harmful effects which should be properly evaluated prior to their use.

Antioxidant and anti-genotoxic properties of cerium oxide nanoparticles in a pulmonary-like cell system

“…Finally, cell line characteristics such as p53 status or tumoral origin can also influence the role of CeO 2 -NP as cytotoxic ) by accumulating hydroxyl ions over superoxide radicals in acidic pH potentiating cancer cell apoptosis, due to its valence-state oscillations (Asati et al 2009). In this context, a recent study showed data in a tumoral lung cell line (A549) wherein apoptotic cell death via ROS-mediated DNA damage and cell cycle arrest, as well as morphological changes, were observed (Mittal and Pandey 2014). This would emphasize the importance of the cell line used to determine the toxicity of NP, including CeO 2 -NP.…”

Hot Topics and Challenges of Regenerative Nanoceria in Application of Antioxidant Therapy

“…From this result, it has been found that nanoceria had the ability of free-radical scavenging, which created a precedent of nanoceria in biological applications and greatly inspired the people of research interest. Until now, there have been many studies on the toxicity properties of nanoceria coated with polymers (dextran, PEG, chitosan, heparin, PAA, and PVP) within the range of 3-20 nm as demonstrated in Figure 4 against cancer cells (lung, breast, ovary, osteosarcoma, and pancreas) and healthy cells (dermal fibroblasts, endothelial cell, keratinocytes, human monocytes, and macrophages) [25][26][27][28][29]. All these researches have laid a foundation for study of antioxidant property.…”

Functional Recovery of Contused Spinal Cord in Rat with the Injection of Optimal‐Dosed Cerium Oxide Nanoparticles

“…CONPs have also shown to be effective in protecting adult cardiac progenitor cells against ROS‐induced stress,9 and in reducing inflammation and radiation‐induced damage in internal organs in mice 10. On the other hand, some studies have reported controversial effects of CONPs; when applied to human lung epithelial cells, adverse cellular responses including increased ROS, induction of oxidative‐stress genes, and apoptotic cell death were observed 11. This is primarily due to the different (possibly higher) doses used and the variable oxidation/reduction state of the CONPs as well as the cell‐dependent responses of nanoparticles such as endocytic activity and toxicity sensitivity.…”