Tryptone-stabilized gold nanoparticles induce unipolar clustering of supernumerary centrosomes and G1 arrest in triple-negative breast cancer cells

J. Grace Nirmala,Manu Lopus

doi:10.1038/s41598-019-55555-3

Abstract

Gold nanoparticles of different sizes, shapes, and decorations exert a variety of effects on biological systems. We report a novel mechanism of action of chemically modified, tryptone-stabilized gold nanoparticles (T-GNPs) in the triple-negative breast cancer (TNBC) cell line, MDA-MB-231. The T-GNPs, synthesized using HAuCl4.3H2O and tryptone and characterized by an assortment of spectroscopy techniques combined with high-resolution electron microscopy, demonstrated strong antiproliferative and anti-clonogenic potential against MDA-MB-231 cells, arresting them at the G1 phase of the cell cycle and promoting apoptosis. The molecular mechanism of action of these particles involved induction of unipolar clustering and hyper amplification of the supernumerary centrosomes (a distinctive feature of many tumour cells, including TNBC cells). The clustering was facilitated by microtubules with suppressed dynamicity. Mass spectrometry-assisted proteomic analysis revealed that the T-GNP-induced G1 arrest was facilitated, at least in part, by downregulation of ribosome biogenesis pathways. Due to the presence of supernumerary centrosomes in many types of tumour cells, we propose chemical induction of their unipolar clustering as a potential therapeutic strategy.

Highlights

Gold nanoparticles of different sizes, shapes, and decorations exert a variety of effects on biological systems
This study reports a novel mechanism of action of the tryptone-stabilized gold nanoparticles (T-GNPs) that involves the supernumerary centrosomes of the triple-negative breast cancer (TNBC) cell line, MDA-MB-231
The functional groups of tryptone involved in the reduction of Au3+ and the capping molecules on the synthesized T-GNPs were verified by Fourier-transform infrared (FTIR) analysis (Fig. 1E)

Summary

Introduction

Gold nanoparticles of different sizes, shapes, and decorations exert a variety of effects on biological systems. We report a novel mechanism of action of chemically modified, tryptone-stabilized gold nanoparticles (T-GNPs) in the triple-negative breast cancer (TNBC) cell line, MDA-MB-231. Due to the presence of supernumerary centrosomes in many types of tumour cells, we propose chemical induction of their unipolar clustering as a potential therapeutic strategy. Microtubules are dynamic cytoskeletal polymers in eukaryotic cells that take part in several functions, including the positioning and maintenance of centrosomes and providing structural stability to the cell[12,13]. These cytoskeletal filaments are generated by the reversible addition of a double-subunit protein, tubulin. In order to overcome dose-limiting and off-target toxicities that are associated with current chemotherapeutics, it is imperative to develop potential therapeutic candidates that can eliminate cancer cells by exploiting their differential constitution

Methods

Results

Conclusion