Metal oxides (MeOx) are exponentially being used in a wide range of applications and are the largest class of commercially produced nanomaterials. This presents unprecedented human exposure. Thus, understanding nanoparticle induced cellular stress can greatly help design strategies to combat them. Scores of studies have been carried out to understand the effects of MeOx nanoparticle exposure on human alveolar cells, which are highly susceptible to aerosolized matter. There is a huge redundancy of information generated, also, a lack of a comprehensive conglomeration of this information. We have built here in a sincere summary of the cellular responses reported till date as a direct consequence of MeOx nanoparticle exposure on human alveolar (A549) cells. Detailed accounts of cellular morphology modulation, generation of reactive oxygen species (ROS) and oxidative stress, inflammation and cytokine release, genotoxic and epi-genotoxic insults, toxicological trend, nanoparticle internalization, modes of cell death, protein synthesis, and membrane damage among others are discussed. Finally, to aid predictability of the highly dynamic and multifactorial nature of this toxicity, we have hypothesized models that describe the ensuing mechanisms based on common patterns discovered throughout our literature survey.
Background: Quinacrine (QC) is popular for its anti-malarial activity. It has been reported exhibiting anti-cancerous properties by suppressing nuclear factor-κB and activating p53 signaling; however, its effect on cellular pathways in human non-small cell lung cancer (NSCLC) has not been studied. Materials and Methods: Binding of QC with GSTA1 was studied computationally as well as through GST activity assay kit. Cell viability, cell cycle and mitochondrial membrane potential activity were studied using flow cytometry. RT-PCR and western blot were carried out to understand the involvement of various genes at their mRNA as well as protein level. Results: QC inhibited the activity of GSTA1 approximately by 40-45% which inhibits cell survival and promotes apoptosis. QC reduced viability of NSCLC cells in a dose-dependent manner. It also causes nuclear fragmentation, G 1 /S arrest of cell cycle and ROS generation; which along with disruption of mitochondrial membrane potential activity leads to apoptotic fate. Conclusions: Results revealed, QC has promising anti-cancer potential against NSCLC cells via inhibition of GSTA1, induction of G 1 /S arrest and ROS mediated apoptotic signaling.
Type II alveolar cells are highly robust in nature, yet susceptible to aerosolized nanoparticles (NPs). Dysfunction in these specialized cells, can often lead to emphysema, edema, and pulmonary inflammation. Long-time exposure can also lead to dangerous epigenetic modifications and cancer. Among the manufactured nanomaterials, metal oxide nanoparticles are widely encountered owing to their wide range of applications. Scores of published literatures affirm ZnO NPs are more toxic to human alveolar cells than TiO2. However, signalling cascades deducing differences in human alveolar responses to their exposure is not well documented. With A549 cells, we have demonstrated that epithelial to mesenchymal transition and an increased duration of phosphorylation of eIF2α are crucial mechanisms routing better tolerance to TiO2 NP treatment over exposure to ZnO. The increased migratory capacity may help cells escape away from the zone of stress. Further, expression of chaperone such as Hsp70 is also enhanced during the same dose-time investigations. This is the first report of its kind. These novel findings could be successfully developed in the future to design relief strategies to alleviate metal oxide nanoparticle mediated stress.
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