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 AgNO₃ 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.

• Caco-2
• in vitro
• MCF-7
• silver nanoparticles
• toxicogenomics

Acknowledgements

The authors would like to thank D. Scholz, T. O'Neill and G. Vaz (Conway Institute of Biomolecular and Biomedical Research, University College Dublin) for their excellent expertise and assistance with the TEM and CM analyses.

Declaration of interest

The authors have no conflicts of interest to declare.

This research was in part supported by the European Commission 7th framework project QualityNano Transnational Access Facilities grant (QualityNano Grant Agreement No. 262163) and by NanoNextNL, a micro- and nanotechnology consortium of the Government of the Netherlands and 130 partners.

Supplementary material available online