NF-\u03baB-related decrease of glioma angiogenic potential by graphite nanoparticles and graphene oxide nanoplatelets

Mateusz Wierzbicki,Marta Grodzik,Ewa Sawosz,Sławomir Jaworski,Barbara Strojny,André Chwalibog

doi:10.1038/s41598-018-33179-3

Mateusz Wierzbicki, Marta Grodzik + Show 4 more

Open Access

https://doi.org/10.1038/s41598-018-33179-3

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Abstract

Gliomas develop an expanded vessel network and a microenvironment characterized by an altered redox environment, which produces high levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that fuel its growth and malignancy. ROS and RNS can influence tumor cell malignancy via the redox-regulated transcription factor NF-κB, whose activation is further regulated by the mutation status of p53. The objective of this study was to assess the influence of graphite nanoparticles (NG) and graphene oxide nanoplatelets (nGO) on the angiogenic potential of glioma cell lines with different p53 statuses. Nanoparticle treatment of glioma cells decreased the angiogenesis of human umbilical vein endothelial cells (HUVEC) cocultured with U87 (p53 wild type) and was not effective for U118 (p53 mutant) cells. Nanoparticle activity was related to the decreased level of intracellular ROS and RNS, which downregulated NF-κB signaling depending on the p53 status of the cell line. Activation of NF-κB signaling affected downstream protein levels of interleukin 6, interleukin 8, growth-regulated oncogene α, and monocyte chemotactic protein 1. These results indicate that the activity of NG and nGO can be regulated by the mutation status of glioma cells and therefore give new insights into the use of nanoparticles in personalized biomedical applications regarding glioma angiogenesis and its microenvironment.

Highlights

Gliomas, which are some of the most common malignant tumors of the central nervous system, develop a microenvironment that is characterized by an altered redox state and an abundance of proangiogenic and proinflammatory factors[1]
It was suggested that carbon nanoparticles (i.e., NG and nGO) could influence other basic physiological activities of glioma cells and that the process of blood vessel growth toward the tumor should be assessed
This study has shown, for the first time, that NG and nGO can influence the angiogenic potential of glioma cells and that the response of glioma cells to carbon nanoparticle treatment can be dependent on p53 status related to NF-κB activity

Summary

Introduction

Gliomas, which are some of the most common malignant tumors of the central nervous system, develop a microenvironment that is characterized by an altered redox state and an abundance of proangiogenic and proinflammatory factors[1]. Tumor cells, including gliomas, maintain an altered redox environment with high production of ROS and RNS that causes tumorigenic cell signaling[4]. ROS and RNS influence tumor cell malignancy in different ways, but one of the most important is regulation of NF-κB transcription factor activation. NF-κB regulates numerous genes, including those involved in the development of the tumor microenvironment and the synthesis of proangiogenic and proinflammatory cytokines[7]. Tumors with p53 mutations often show gain-of-function phenotypes that usually enhance their malignancy, including enhanced invasiveness and decreased sensitivity to proapoptotic signals[9]. It is assumed that this will decrease NF-κB-dependent proangiogenic cytokines in a p53 wild-type glioma cell line (U87) but not in a p53 mutant cell line (U118)

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