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proteins, proteins involved in regulation of apoptosis, proteins involved in the response to oxidative stress and glycolytic proteins. Figure 8 reports the histograms of protein level variations following the AgNPs-EPSaer treatment, compared with the untreated cells. Interestingly, proteomics results highlights important pathways involved in the mechanism of action of AgNPs-EPSaer on SKBR3 cells and strengthens our previous observations on its biological function. In particular the differentially proteins identified can efficiently explain the cellular effects of AgNPs-EPSaer. Infact accumulating evidence suggests that protein folding and generation of reactive oxygen species (ROS) as a byproduct of protein oxidation in the ER are closely linked events [46]. Persistent oxidative stress and protein misfolding initiate cell death cascades, involving mitochondrial disfunctions; moreover, mitochondrial turnover is dependent on autophagy. Collectively, the dow-regulation of glycolitic enzymes suggest a partial reversion of the so called Warburg effect, first described by Otto Warburg, and considered an important cancer hallmark [47]. Uptake of AgNPs-EPSaer by SKBR3 cells TEM micrographs (Figure 9) showed that AgNPs- EPSaer treated cells exhibited numerous endosomes with Figure 6: Differential proteomic analysis of SKBR3 cells treated with AgNPs-EPS. (A) Proteomic map of SKBR3 control cells. Labels indicate the 253 differential protein spots. (B) Eulero Venn diagram showing the differentially expressed proteins selected on the threshold setting in the studied groups; (C) Histograms showing the up and down-regulated proteins plotted as fold change compared to untreated cells. www.impactjournals.com/oncotarget 9692 OncotargetPDF Image | Anticancer activity of biogenerated silver nanoparticles
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