Effect of Chitosan-Stabilized Selenium Nanoparticles on Cell Cycle Arrest and Invasiveness in Hepatocarcinoma Cells Revealed by Quantitative Proteomics

Isabel Lopez Heras

doi:10.4172/2157-7439.1000226

Abstract

Selenium nanoparticles have been recently proposed as a potential chemotherapeutic agent due to its low toxicity and its ability to arrest the cell cycle of cancer cells. However, the biochemical mechanisms associated to this effect have not yet been uncovered. We evaluate here the potential of chitosan-stabilized selenium nanoparticles to induce cell cycle arrest and to inhibit in-vitro invasiveness in HepG2 cells. In addition, we use a quantitative proteomic approach to identify potential protein targets involved in the mechanisms associated to selenium nanoparticles exposure. Our data suggest that the induction of the cell cycle arrest at the S phase is mediated by de-regulation of the eIF3 protein complex. We found additional de-regulated proteins upon selenium nanoparticles exposure that could also be involved in the overall inhibition of cell proliferation. These findings not only support the potential of chitosan-stabilized selenium nanoparticles as anti-cancer therapy but also provide a deeper insight into the mechanisms associated to their chemotherapeutic effects.

Highlights

Selenium is one of the essential trace elements and has great importance in nutrition and medicine due to its antioxidant properties
The size distribution was significantly affected by the concentration of chitosan. 0.1% chitosan provided a homogeneous dispersion in which around 80-90% of the Ch-Selenium nanoparticles (SeNPs) had a size in the range 40-60 nm (Figure 1A) and we selected this concentration for further experiments
The similar cell cycle pattern among transfected cells and cells exposed to Ch-SeNPs together with the different level of expression found for eukaryotic translation initiation factor 3 (eIF3) subunits after Ch-SeNPs exposure that we showed previously, support the hypothesis that ChSeNPs induce eIF3-mediated cell cycle arrest (Figures 6A and 6B)

Summary

Introduction

Selenium is one of the essential trace elements and has great importance in nutrition and medicine due to its antioxidant properties. It has been reported that SeNPs exhibit a great selectivity between cancer and normal cells showing a broad spectrum of growth inhibition for A375, CNE2, MCF-7 and HepG2 cancer cells This effect was more pronounced than when using Se IV at a similar concentration [6]. It has been shown the anti-proliferative effect of SeNPs on HeLa, MDA-MB-231 and HepG2 cells in a dosedependent manner by induction of cell cycle arrest [7,8]. The biomolecular mechanisms involved in this inhibitory effect have not yet been fully understood

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