Different responses of Caco-2 and MCF-7 cells to silver nanoparticles are based on highly similar mechanisms of action

Abstract

The mode of action of silver nanoparticles (AgNPs) is suggested to be exerted through both Ag + and AgNP dependent mechanisms. Ingestion is one of the major NP exposure routes, and potential effects are often studied using Caco-2 cells, a well-established model for the gut epithelium. MCF-7 cells are epithelial breast cancer cells with extensive well-characterized toxicogenomics profiles. In the present study, we aimed to gain a deeper understanding of the cellular molecular responses in Caco-2 and MCF-7 cells after AgNP exposure in order to evaluate whether epithelial cells derived from different tissues demonstrated similar responses. These insights could possibly reduce the size of cell panels for NP hazard identification screening purposes. AgNPs of 20, 30, 60, and 110 nm, and AgNO 3 were exposed for 6 h and 24 h. AgNPs were shown to be taken up and dissolve intracellularly. Compared with MCF-7 cells, Caco-2 cells showed a higher sensitivity to AgNPs, slower gene expression kinetics and absence of NP size-dependent responses. However, on a molecular level, no significant differences were observed between the two cell types. Transcriptomic analysis showed that Ag(NP) exposure caused (oxidative) stress responses, possibly leading to cell death in both cell lines. There was no indication for effects specifically induced by AgNPs. Responses to AgNPs appeared to be induced by silver ions released from the AgNPs. In conclusion, differences in mRNA responses to AgNPs between Caco-2 and MCF-7 cells were mainly related to timing and magnitude, but not to a different underlying mechanism.

Intracellular Antioxidant Activity of Biocompatible Citrate-Capped Palladium Nanozymes

“…In particular, we found a cell type-dependent internalization of nanoparticles, because Caco-2 cells endocytosed circa one tenth of the particles internalized by HeLa cells ( Supplementary Table S1), likely due to their different cell body dimensions. This is in qualitative agreement with previous studies with other metal NPs [39,63]. We then imaged by TEM the subcellular localization of PdNPs in HeLa cells, upon exposure to Pd4 and Pd8 for 24 h. As shown in Figure 5 and in Supporting Figure S1, NPs were internalized in cells by the endo-lysosomal pathway and confined into late endosomal and/or lysosomal compartments.…”

Silver nanoparticles selectively treat triple‐negative breast cancer cells without affecting non‐malignant breast epithelial cells in vitro and in vivo

“…77 Comparative studies by Bouwmeester and colleagues on gene expression following sub-lethal AgNP exposure in Caco-2 and MCF-7 cells found that pathways connected to oxidative stress, responses to metal ions, or cell division were activated in both cell lines. 78 Although Caco-2 cells showed a higher sensitivity to AgNPs than MCF-7 cells, no differences were observed between the two cell types related to which pathways were activated, but differences were observed in timing and magnitude, with responses being greater and more rapid in Caco-2 cells as compared to MCF-7 cells. The authors further noted that Caco-2 cells appeared to have higher baseline stress levels than the MCF-7 cells.…”

Combination of the BeWo b30 placental transport model and the embryonic stem cell test to assess the potential developmental toxicity of silver nanoparticles

“…Besides, the cellular compartment contained a lower AgNPs percentage (of the total Ag content) compared to the AgNPs percentage in the exposure concentration in the apical compartment. This suggests a preference towards cellular uptake/association of ionic silver over AgNPs or possible dissolution of the AgNPs cellularly following their uptake [44][45][46].…”