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Silica nanoparticle-induced oxidative stress and mitochondrial damage is followed by activation of intrinsic apoptosis pathway in glioblastoma cells

Overview of attention for article published in International Journal of Nanomedicine, April 2018
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Title
Silica nanoparticle-induced oxidative stress and mitochondrial damage is followed by activation of intrinsic apoptosis pathway in glioblastoma cells
Published in
International Journal of Nanomedicine, April 2018
DOI 10.2147/ijn.s158393
Pubmed ID
Authors

Magdalena Kusaczuk, Rafał Krętowski, Monika Naumowicz, Anna Stypułkowska, Marzanna Cechowska-Pasko

Abstract

Recently, the focus of oncological research has been on the optimization of therapeutic strategies targeted at malignant diseases. Nanomedicine utilizing silicon dioxide nanoparticles (SiNPs) is one such strategy and is rapidly developing as a promising tool for cancer diagnosis, imaging, and treatment. Nevertheless, little is known about the mechanisms of action of SiNPs in brain tumors. Here, we explored the effects of 5-15 nm SiNPs in the human glioblastoma cell line LN229. In this respect, MTT assays, microscopic observations, flow cytometry analyses, and luminescent assays were performed. Moreover, RT-qPCR and Western blot analyses were done to determine gene and protein expressions. We demonstrated that SiNPs triggered evident cytotoxicity, with microscopic observations of the nuclei, annexin V-fluorescein isothiocyanate/propidium iodide staining, and elevated caspase 3/7 activity, suggesting that SiNPs predominantly induced apoptotic death in LN229 cells. We further showed the occurrence of oxidative stress induced by enhanced reactive oxygen-species generation. This effect was followed by deregulated expression of genes encoding the antioxidant enzymes SOD1, SOD2, and CAT, and impaired mitochondria function. SiNP- induced mitochondrial dysfunction was characterized by membrane-potential collapse, ATP depletion, elevated expression of BAX, PUMA, and NOXA with simultaneous downregulation of BCL2/BCL2L1, and activation of caspase 9. Moreover, RT-qPCR and Western blot analyses demonstrated increased levels of the endoplasmic reticulum stress markers GRP78, GRP94, and DDIT3, as well as strongly increased expressions of the IL1B and COX2 genes, suggesting activation of endoplasmic reticulum stress and a proinflammatory response. Altogether, our data indicate that in LN229 cells, SiNPs evoke cell death via activation of the intrinsic apoptosis pathway and suggest that other aspects of cellular function may also be affected. As such, SiNPs represent a potentially promising agent for facilitating further progress in brain cancer therapy. However, further exploration of SiNP long-term toxicity and molecular effects is necessary prior to their widespread application.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 45 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 13 29%
Student > Bachelor 8 18%
Student > Master 7 16%
Student > Doctoral Student 3 7%
Researcher 3 7%
Other 4 9%
Unknown 7 16%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 13 29%
Medicine and Dentistry 5 11%
Pharmacology, Toxicology and Pharmaceutical Science 3 7%
Chemistry 3 7%
Agricultural and Biological Sciences 2 4%
Other 7 16%
Unknown 12 27%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 April 2018.
All research outputs
#10,246,933
of 12,834,493 outputs
Outputs from International Journal of Nanomedicine
#1,953
of 2,508 outputs
Outputs of similar age
#203,137
of 269,449 outputs
Outputs of similar age from International Journal of Nanomedicine
#31
of 42 outputs
Altmetric has tracked 12,834,493 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,508 research outputs from this source. They receive a mean Attention Score of 3.0. This one is in the 10th percentile – i.e., 10% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 269,449 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 42 others from the same source and published within six weeks on either side of this one. This one is in the 9th percentile – i.e., 9% of its contemporaries scored the same or lower than it.