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Silica Nanoparticles Provoke Cell Death Independent of p53 and BAX in Human Colon Cancer Cells

Fritsch-Decker, Susanne; An, Zhen; Yan, Jin; Hansjosten, Iris; Al-Rawi, Marco; Peravali, Ravindra; Diabaté, Silvia; Weiss, Carsten

Several in vitro studies have suggested that silica nanoparticles (NPs) might induce adverse effects in gut cells. Here, we used the human colon cancer epithelial cell line HCT116 to study the potential cytotoxic effects of ingested silica NPs in the presence or absence of serum. Furthermore, we evaluated different physico-chemical parameters important for the assessment of nanoparticle safety, including primary particle size (12, 70, 200, and 500 nm) and surface modification (–NH2 and –COOH). Silica NPs triggered cytotoxicity, as evidenced by reduced metabolism and enhanced membrane leakage. Automated microscopy revealed that the silica NPs promoted apoptosis and necrosis proportional to the administered specific surface area dose. Cytotoxicity of silica NPs was suppressed by increasing amount of serum and surface modification. Furthermore, inhibition of caspases partially prevented silica NP-induced cytotoxicity. In order to investigate the role of specific cell death pathways in more detail, we used isogenic derivatives of HCT116 cells which lack the pro-apoptotic proteins p53 or BAX. In contrast to the anticancer drug cisplatin, silica NPs induced cell death independent of the p53–BAX axis. ... mehr

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Verlagsausgabe §
DOI: 10.5445/IR/1000097786
Veröffentlicht am 18.09.2019
DOI: 10.3390/nano9081172
Zitationen: 2
Web of Science
Zitationen: 3
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2019
Sprache Englisch
Identifikator ISSN: 2079-4991
KITopen-ID: 1000097786
HGF-Programm 47.01.01 (POF III, LK 01)
Biol.Netzwerke u.Synth.Regulat. ITG+ITC
Erschienen in Nanomaterials
Band 9
Heft 8
Seiten 1172
Vorab online veröffentlicht am 16.08.2019
Schlagwörter synthetic amorphous silica, nanoparticles; colon cells, in vitro toxicity, cell death
Nachgewiesen in Web of Science
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