Reduced Graphene Oxides Modulate the Expression of Cell Receptors and Voltage-Dependent Ion Channel Genes of Glioblastoma Multiforme.

Jaroslaw Szczepaniak,Dorota Nowak,Mateusz Wierzbicki,Barbara Strojny-Cieslak,Maciej Szmidt,Slawomir Jaworski,Anna Sobczyk-Guzenda,Olga Witkowska-Pilaszewicz,Karolina Daniluk,Malwina Sosnowska,Joanna Jagiello,Marta Grodzik

doi:10.3390/ijms22020515

Abstract

The development of nanotechnology based on graphene and its derivatives has aroused great scientific interest because of their unusual properties. Graphene (GN) and its derivatives, such as reduced graphene oxide (rGO), exhibit antitumor effects on glioblastoma multiforme (GBM) cells in vitro. The antitumor activity of rGO with different contents of oxygen-containing functional groups and GN was compared. Using FTIR (fourier transform infrared) analysis, the content of individual functional groups (GN/exfoliation (ExF), rGO/thermal (Term), rGO/ammonium thiosulphate (ATS), and rGO/ thiourea dioxide (TUD)) was determined. Cell membrane damage, as well as changes in the cell membrane potential, was analyzed. Additionally, the gene expression of voltage-dependent ion channels (clcn3, clcn6, cacna1b, cacna1d, nalcn, kcne4, kcnj10, and kcnb1) and extracellular receptors was determined. A reduction in the potential of the U87 glioma cell membrane was observed after treatment with rGO/ATS and rGO/TUD flakes. Moreover, it was also demonstrated that major changes in the expression of voltage-dependent ion channel genes were observed in clcn3, nalcn, and kcne4 after treatment with rGO/ATS and rGO/TUD flakes. Furthermore, the GN/ExF, rGO/ATS, and rGO/TUD flakes significantly reduced the expression of extracellular receptors (uPar, CD105) in U87 glioblastoma cells. In conclusion, the cytotoxic mechanism of rGO flakes may depend on the presence and types of oxygen-containing functional groups, which are more abundant in rGO compared to GN.

Highlights

Glioblastoma (GBM) is the most common primary malignant brain tumor
Different types of graphene derivatives may activate separate cell pathways. reduced graphene oxide (rGO) can affect cells as the result of contact with the glioblastoma cell membrane via its functional groups, which are presented on the surface of the examined flakes
This is the first study confirming that graphene flakes have a significant effect on the expression of voltage-dependent ion channel (VGIC) genes in U87 glioma cells

Summary

Introduction

Glioblastoma (GBM) is the most common primary malignant brain tumor. GBM is associated with poor prognosis and a life expectancy of approximately 15 months despite optimal therapy, which includes surgery, chemotherapy, and radiotherapy [1]. Graphene is made up of a layer of carbon atoms arranged in a hexagonal pattern and consists purely of sp hybridized bonds. It has gained enormous interest in various fields owing to its unique electrochemical properties, which include high thermal conductivity, high current, density, chemical volume, optical transmittance, and very high hydrophobicity [3,4]. It is the simplest form of carbon and the thinnest material ever produced [5]

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