Identification of the Nanogold Particle-Induced Endoplasmic Reticulum Stress by Omic Techniques and Systems Biology Analysis

Abstract

Growth inhibition and apoptotic/necrotic phenotype was observed in nanogold particle (AuNP)-treated human chronic myelogenous leukemia cells. To elucidate the underlying cellular mechanisms, proteomic techniques including two-dimensional electrophoresis/mass spectrometry and protein microarrays were utilized to study the differentially expressed proteome and phosphoproteome, respectively. Systems biology analysis of the proteomic data revealed that unfolded protein-associated endoplasmic reticulum (ER) stress response was the predominant event. Concomitant with transcriptomic analysis using mRNA expression, microarrays show ER stress response in the AuNP-treated cells. The ER stress protein markers' expression assay unveiled AuNPs as an efficient cellular ER stress elicitor. Upon ER stress, cellular responses, including reactive oxygen species increase, mitochondrial cytochrome c release, and mitochondria damage, chronologically occurred in the AuNP-treated cells. Conclusively, this study demonstrates that AuNPs cause cell death through induction of unmanageable ER stress.

Inhibition of colon cancer cell growth by nanoemulsion carrying gold nanoparticles and lycopene

“…In a similar study dealing with the effect of various sized AN on the cytotoxicity of leukemia cell, k562, the following order was observed: 1-3 nm 5-6 nm 15-20 nm. 20 Thus, the size of 3-5 nm AN used in our experiment should be able to penetrate into HT-29 cells to induce apoptosis or necrosis.…”

“…These nanoparticles were prepared by a molecular beam epitaxy process, as previously reported. 20 Briefly, bulk gold material was cut and ground, followed by vaporization with an ultrahigh vacuum (10 -8 Pa) to its atomic state and condensation in the presence of inert gas to form AN. The concentration of AN was determined using an inductively coupled plasma mass spectrometer (PerkinElmer-SCIEX ELAN 6100 DRC; PerkinElmer, Inc., Waltham, MA, USA).…”

“…The concentration of AN was determined using an inductively coupled plasma mass spectrometer (PerkinElmer-SCIEX ELAN 6100 DRC; PerkinElmer, Inc., Waltham, MA, USA). 20 …”

“…Consistent with the previous evidence on high host toxicity for 1-3 nm AN and low efficiency for 10-15 nm AN, the particle size of AN at 3-5 nm was selected for subsequent experiments. 20 The IC 50 for LP alone was 16.8 µM ( Figure 2B), and thus a low dose below IC 50 of AN or LP alone or in combination was then tested for its efficiency in inducing the cytotoxicity of HT-29 cells. As shown in Figure 2C, AN at 10 ppm in combination with LP at 8 µM or 12 µM (AN+LP combo treatment) exerted a synergistic effect, as shown by a reduction of 50-60% viability of the HT-29 cells.…”

The bio-nano-interface in predicting nanoparticle fate and behaviour in living organisms: towards grouping and categorising nanomaterials and ensuring nanosafety by design

“…However, as with many early studies in an emerging field, there are some concerns regarding how much can be interpreted from this study which lacked appropriate controls [e.g., no bulk TiO 2 or other (reference) material has been used for comparison]. Another example of this approach uses proteomic techniques including two-dimensional electrophoresis/ mass spectrometry and protein microarrays to study the differentially expressed proteome and phosphoproteome, respectively [115]. Here, systems biology analysis of the data revealed that unfolded protein-associated endoplasmic reticulum (ER) stress response was the predominant event in response to the presence of gold nanoparticles [115].…”