Gold nanoparticles-induced cytotoxicity in triple negative breast cancer involves different epigenetic alterations depending upon the surface charge

Abstract

Gold nanoparticles (AuNPs) are used enormously in different cancers but very little is known regarding their molecular mechanism and surface charge role in the process of cell death. Here, we elucidate the molecular mechanism by which differentially charged AuNPs induce cytotoxicity in triple negative breast cancer (TNBC) cells. Cytotoxicity assay revealed that both negatively charged (citrate-capped) and positively charged (cysteamine-capped) AuNPs induced cell-death in a dose-dependent manner. We provide first evidence that AuNPs-induced oxidative stress alters Wnt signalling pathway in MDA-MB-231 and MDA-MB-468 cells. Although both differentially charged AuNPs induced cell death, the rate and mechanism involved in the process of cell death were different. Negatively charged AuNPs increased the expression of MKP-1, dephosphorylated and deacetylated histone H3 at Ser10 and K9/K14 residues respectively whereas, positively charged AuNPs decreased the expression of MKP-1, phosphorylated and acetylated histone H3 at Ser 10 and K9/K14 residues respectively. High-resolution transmission electron microscopy (HRTEM) studies revealed that AuNPs were localised in cytoplasm and mitochondria of MDA-MB-231 cells. Interestingly, AuNPs treatment makes MDA-MB-231 cells sensitive to 5-fluorouracil (5-FU) by decreasing the expression of thymidylate synthetase enzyme. This study highlights the role of surface charge (independent of size) in the mechanisms of toxicity and cell death.

Application of Oil-in-Water Nanoemulsion Carrying Size-Defined Gold Nanoparticles Synthesized by Non-thermal Plasma for the Human Breast Cancer Cell Lines Migration and Apoptosis

“…These results showed that AuNPs-loaded nanoemulsion (group VI) could inhibit the proliferation of the invasive breast cancer cells and did not moderate the non-invasive cancer cells as well as the non-transformed breast cells. Similar results were reported by other researchers, who observed the inhibition of the breast cancer cells treated with the AuNPs [62,63]. However, in our study it was observed that the proliferation activity of the human cancer invasive cells was selectively inhibited Table 2).…”

A new strategy for the green synthesis of chondroitin sulfate-reduced gold nanoparticles; in vitro evaluation of synthesized nanoparticles

“…They attributed the cytotoxicity effects of GNPs to the generation of oxidative stress in a dose-dependent manner in cancer cell lines; cysteamine-capped GNPs showed more oxidative stress in comparison to citrate-capped GNPs, while no oxidative stress was generated by GNPs in normal cells. 35 Furthermore, the cytotoxicity of citrate-capped GNPs (20 nm) on the MRC-5 human fetal lung fibroblast cell line at different concentrations of studied by Li et al, where, they did not observe a significant difference in the percentage of cell death between the treatment and control groups after 24, 48, and 72 hours incubation, which confirms our founding on selective cytotoxicity of GNPs in cancer cells. 36 Different mechanisms have been considered for GNPs' cytotoxicity; GNPs can induce diverse types of cell death through reactive oxygen species (ROS) production and mitochondrial function disturbance.…”

The Effect of Stabilisation Agents on the Immunomodulatory Properties of Gold Nanoparticles Obtained by Ultrasonic Spray Pyrolysis

“…Studies have shown that GNPs' toxicity depends on their size, shape, surface charge, stabilising agent, etc. [18,19,41]. In this context, we showed previously that USP-generated GNPs made of pure gold do not affect the viability of cells in sizes 20-100 nm [29,36].…”