Abstract

Nanostructured silica particles are commonly used in biomedical and biotechnical fields, as well as, in cosmetics and food industry. Thus, their environmental and health impacts are of great interest and effects after oral uptake are only rarely investigated. In the present study, the toxicological effects of commercially available nano-scaled silica with a nominal primary diameter of 12 nm were investigated on the human gastric carcinoma cell line GXF251L. Besides the analysis of cytotoxic and proliferative effects and the comparison with effects of particles with a nominal primary diameter of 200 nm, emphasis was also given to their influence on the cellular epidermal growth factor receptor (EGFR) and mitogen-activated protein kinases (MAPK) signaling pathways—both of them deeply involved in the regulation of cellular processes like cell cycle progression, differentiation or proliferation. The investigated silica nanoparticles (NPs) were found to stimulate cell proliferation as measured by microscopy and the sulforhodamine B assay. In accordance, the nuclear level of the proliferation marker Ki-67 was enhanced in a concentration-dependent manner. At high particle concentrations also necrosis was induced. Finally, silica NPs affected the EGFR and MAPK pathways at various levels dependent on concentration and time. However, classical activation of the EGFR, to be reflected by enhanced levels of phosphorylation, could be excluded as major trigger of the proliferative stimulus. After 45 min of incubation the level of phosphorylated EGFR did not increase, whereas enhanced levels of total EGFR protein were observed. These results indicate interference with the complex homeostasis of the EGFR protein, whereby up to 24 h no impact on the transcription level was detected. In addition, downstream on the level of the MAP kinases ERK1/2 short term incubation appeared to affect total protein levels without clear increase in phosphorylation. Depending on the concentration range, enhanced levels of ERK1/2 phosphorylation were only observed after 24 h of incubation. Taken together, the present study demonstrates the potential of the tested silica particles to enhance the growth of gastric carcinoma cells. Although interference with the EGFR/MAPK cascade is observed, additional mechanisms are likely to be involved in the onset of the proliferative stimulus.

Highlights

  • Besides nanoparticles composed of titanium oxide, aluminum oxide, carbon and other materials, silica nanoparticles (SiO2 NPs) are among the most widely produced [1]

  • The gastric cell line GXF251L and its responses to SiO2 NPs including the influences on viability and possibly cell line GXF251L and its responses to SiO2 NPs including the influences on viability and possibly related signaling cascades were examined

  • Properties and the cellular uptake of the tested particles has been published previously by Gehrke et Thereby, the influence of, inter alia, the same particles on HT29 cells cultured in Dulbecco’s Modified Eagle Media (DMEM) under al. [28]

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Summary

Introduction

Besides nanoparticles composed of titanium oxide, aluminum oxide, carbon and other materials, silica nanoparticles (SiO2 NPs) are among the most widely produced [1]. SiO2 NPs find use in cosmetics, e.g., in toothpaste or skin care products, and within the food sector. In more detail, they can be found as food additives (E551) like anticaking agents in salt, spices or instant soups, as flavor enhancers or food pigments, as coating material in confectionary products and packaging materials or as health supplements [12,13,14,15,16,17]. Previous studies of SiO2 NPs mainly focused on inhalational exposure [1,2,18,19,20]. Studies on the oral route of exposure are progressively increasing and more data have recently become available

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