Treatment of human astrocytoma U87 cells with silicon dioxide nanoparticles lowers their survival and alters their expression of mitochondrial and cell signaling proteins

Abstract

Recent evidence suggests silicon dioxide micro- and nanoparticles induce cytotoxic effects on lung cells. Thus, there is an increasing concern regarding their potential health hazard. Nevertheless, the putative toxicity of nanoparticles in mammalian cells has not yet been systematically investigated. We previously noted that several metallic oxide nanoparticles exert differential cytotoxic effects on human neural and nonneural cells. Therefore, we hypothesized that silicon dioxide nanoparticles induce cytotoxicity in U87 cells by lowering their survival by decreasing cell survival signaling and disturbing mitochondrial function. To investigate this hypothesis, we determined the activities of the key mitochondrial enzymes, citrate synthase and malate dehydrogenase, in astrocytoma U87 cells treated with silicon dioxide nanoparticles. In addition, we studied the expression of the mitochondrial DNA-encoded proteins, cytochrome C oxidase II and nicotinamide adenine dinucleotide (NADPH) dehydrogenase subunit 6, and cell signaling pathway protein extracellular signal-regulated kinase (ERK) and phosphorylated ERK in treated U87 cells. The activated form of ERK controls cell growth, differentiation, and proliferation. In parallel, we determined survival of U87 cells after treating them with various concentrations of silicon dioxide nanoparticles. Our results indicated that treatment with silicon dioxide nanoparticles induced decreases in U87 cell survival in a dose-related manner. The activities of citrate synthase and malate dehydrogenase in treated U87 cells were increased, possibly due to an energetic compensation in surviving cells. However, the expression of mitochondrial DNA-encoded cytochrome C oxidase subunit II and NADH dehydrogenase subunit 6 and the cell signaling protein ERK and phosphorylated ERK were altered in the treated U87 cells, suggesting that silicon dioxide nanoparticles induced disruption of mitochondrial DNA-encoded protein expression, leading to decreased mitochondrial energy production and decreased cell survival/proliferation signaling. Thus, our results strongly suggest that the cytotoxicity of silicon dioxide nanoparticles in human neural cells implicates altered mitochondrial function and cell survival/proliferation signaling.

Interactions Between Nanosized Materials and the Brain

“…In addition, the treatment had negative effects on the NGF-induced differentiation where number of neurites/cell, neurite length, and intercellular contacts/cell all decreased as a function of dose. A similar effect on survival was seen in the work by Lai et al [ 79 ] where U87 astrocytoma cells were exposed for 48 h to 12 nm SiO 2 NP. A dose-dependent decrease in cell survival was seen at ≥ 25µg/ml, accompanied by an increased activity of two mitochondrial enzymes and decreased levels of certain mitochondrial proteins and decreased ERK signaling.…”

“…Both Wang et al [ 78 ] and Lai et al [ 79 ] investigated effects of SiO 2 NPs on cell survival and other end-points in two human cell lines with origin in the nervous system. The work by Wang et al employed NGF-treated PC12 cells that were subjected to 20 and 50 nm SiO 2 NPs for 12-48 h. The treatment caused a concentration and time-dependent decrease in cell survival which seemed to be mediated by increased oxidative stress.…”

Effects and mechanism of amyloid β1-42 on mitochondria in astrocytes

“…Various reports have indicated that U87 human glioblastoma cells may be used as astrocytes for AD neuropathology and cytotoxicity studies ( 19 – 21 ). As a cellular marker of astrocytes, GFAP (green staining) was highly expressed on U87 cells that were not treated with Aβ 1–42 (0 µM group; Fig.…”

Natural Bioactive Compounds: Alternative Approach to the Treatment of Glioblastoma Multiforme

“…Moreover, the surface properties of the nanocarriers can be modified for a selective, controlled drug release with minimal side effects and increased efficacy [ 84 , 94 , 95 ]. Nanomaterial based chemotherapeutic agents such as the liposomes, dendrimers, or polymeric micelles are reported to circumvent the BBB and reach the target site of action [ 87 , 88 , 96 , 97 ]. Several nanomaterials-based drugs have been evaluated for the treatment of GBM and other cancers.…”