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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Jan 9

PMID 33419226

Citations 6

Authors

Jaroslaw Szczepaniak

Joanna Jagiello

Mateusz Wierzbicki

Dorota Nowak

Anna Sobczyk-Guzenda

Malwina Sosnowska

Slawomir Jaworski

Karolina Daniluk

Maciej Szmidt

Olga Witkowska-Pilaszewicz

Barbara Strojny-Cieslak

Marta Grodzik

Affiliations

Soon will be listed here.

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 (, , , , , , , and ) 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 , , and 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.

Citing Articles

Radiosensitizing properties of dual-functionalized carbon nanostructures loaded with temozolomide.

Milenkovska R, Geskovski N, Shalabalija D, Mihailova L, Makreski P, Lukarski D Beilstein J Nanotechnol. 2025; 16:229-251.

PMID: 39995757 PMC: 11849551. DOI: 10.3762/bjnano.16.18.

circ-1584 selectively promotes the antitumor activity of the oncolytic virus M1 on pancreatic cancer.

Hao T, Li Y, Ren Q, Zeng Y, Gao L, Zhu W Mol Ther Oncol. 2025; 33(1):200919.

PMID: 39866243 PMC: 11760297. DOI: 10.1016/j.omton.2024.200919.

Gamma radiation assisted green synthesis of hesperidin-reduced graphene oxide nanocomposite targeted JNK/SMAD4/MMP2 signaling pathway.

Kodous A, Taha E, El-Maghraby D, Hassana A, Atta M Sci Rep. 2024; 14(1):11535.

PMID: 38773159 PMC: 11109164. DOI: 10.1038/s41598-024-60347-5.

Theranostic Applications of 2D Graphene-Based Materials for Solid Tumors Treatment.

Iannazzo D, Celesti C, Giofre S, Ettari R, Bitto A Nanomaterials (Basel). 2023; 13(16).

PMID: 37630966 PMC: 10459055. DOI: 10.3390/nano13162380.

Potential Role of Carbon Nanomaterials in the Treatment of Malignant Brain Gliomas.

Caffo M, Curcio A, Rajiv K, Caruso G, Venza M, Germano A Cancers (Basel). 2023; 15(9).

PMID: 37174040 PMC: 10177363. DOI: 10.3390/cancers15092575.

References

Du J, Haak L, Russell J, McBain C . Frequency-dependent regulation of rat hippocampal somato-dendritic excitability by the K+ channel subunit Kv2.1. J Physiol. 2000; 522 Pt 1:19-31. PMC: 2269745. DOI: 10.1111/j.1469-7793.2000.t01-2-00019.xm. View

Johnstone B . Micro-electrode penetration of ascites tumour cells. Nature. 1959; 183(4658):411. DOI: 10.1038/183411a0. View

Cahoy J, Emery B, Kaushal A, Foo L, Zamanian J, Christopherson K . A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J Neurosci. 2008; 28(1):264-78. PMC: 6671143. DOI: 10.1523/JNEUROSCI.4178-07.2008. View

Ouwerkerk R, Jacobs M, Macura K, Wolff A, Stearns V, Mezban S . Elevated tissue sodium concentration in malignant breast lesions detected with non-invasive 23Na MRI. Breast Cancer Res Treat. 2007; 106(2):151-60. DOI: 10.1007/s10549-006-9485-4. View

Montuori N, Cosimato V, Rinaldi L, Rea V, Alfano D, Ragno P . uPAR regulates pericellular proteolysis through a mechanism involving integrins and fMLF-receptors. Thromb Haemost. 2012; 109(2):309-18. DOI: 10.1160/TH12-08-0546. View

Zhang Y, Cruickshanks N, Yuan F, Wang B, Pahuski M, Wulfkuhle J . Targetable T-type Calcium Channels Drive Glioblastoma. Cancer Res. 2017; 77(13):3479-3490. PMC: 5505315. DOI: 10.1158/0008-5472.CAN-16-2347. View

Geim A, Novoselov K . The rise of graphene. Nat Mater. 2007; 6(3):183-91. DOI: 10.1038/nmat1849. View

Damaghi M, Wojtkowiak J, Gillies R . pH sensing and regulation in cancer. Front Physiol. 2014; 4:370. PMC: 3865727. DOI: 10.3389/fphys.2013.00370. View

Martelli C, King A, Simon T, Giamas G . Graphene-Induced Transdifferentiation of Cancer Stem Cells as a Therapeutic Strategy against Glioblastoma. ACS Biomater Sci Eng. 2021; 6(6):3258-3269. DOI: 10.1021/acsbiomaterials.0c00197. View

10.

Webb B, Chimenti M, Jacobson M, Barber D . Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer. 2011; 11(9):671-7. DOI: 10.1038/nrc3110. View

11.

Poet M, Kornak U, Schweizer M, Zdebik A, Scheel O, Hoelter S . Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6. Proc Natl Acad Sci U S A. 2006; 103(37):13854-9. PMC: 1564226. DOI: 10.1073/pnas.0606137103. View

12.

Lui V, Lung S, Pu J, Hung K, Leung G . Invasion of human glioma cells is regulated by multiple chloride channels including ClC-3. Anticancer Res. 2010; 30(11):4515-24. View

13.

Wen P, Reardon D . Neuro-oncology in 2015: Progress in glioma diagnosis, classification and treatment. Nat Rev Neurol. 2016; 12(2):69-70. DOI: 10.1038/nrneurol.2015.242. View

14.

Arrebola F, Fernandez-Segura E, Campos A, Crespo P, Skepper J, Warley A . Changes in intracellular electrolyte concentrations during apoptosis induced by UV irradiation of human myeloblastic cells. Am J Physiol Cell Physiol. 2005; 290(2):C638-49. DOI: 10.1152/ajpcell.00364.2005. View

15.

Raghu H, Lakka S, Gondi C, Mohanam S, Dinh D, Gujrati M . Suppression of uPA and uPAR attenuates angiogenin mediated angiogenesis in endothelial and glioblastoma cell lines. PLoS One. 2010; 5(8):e12458. PMC: 2929192. DOI: 10.1371/journal.pone.0012458. View

16.

Wang H, Wang W, Liu Y, Li M, Liang T, Li J . Role of KCNB1 in the prognosis of gliomas and autophagy modulation. Sci Rep. 2017; 7(1):14. PMC: 5428316. DOI: 10.1038/s41598-017-00045-7. View

17.

Hoyer-Hansen G, Behrendt N, Ploug M, Dano K, Preissner K . The intact urokinase receptor is required for efficient vitronectin binding: receptor cleavage prevents ligand interaction. FEBS Lett. 1998; 420(1):79-85. DOI: 10.1016/s0014-5793(97)01491-9. View

18.

Aithal M, Rajeswari N . Validation of housekeeping genes for gene expression analysis in glioblastoma using quantitative real-time polymerase chain reaction. Brain Tumor Res Treat. 2015; 3(1):24-9. PMC: 4426273. DOI: 10.14791/btrt.2015.3.1.24. View

19.

Huai Q, Zhou A, Lin L, Mazar A, Parry G, Callahan J . Crystal structures of two human vitronectin, urokinase and urokinase receptor complexes. Nat Struct Mol Biol. 2008; 15(4):422-3. PMC: 2443823. DOI: 10.1038/nsmb.1404. View

20.

Li Y, Um S, McDonald T . Voltage-gated potassium channels: regulation by accessory subunits. Neuroscientist. 2006; 12(3):199-210. DOI: 10.1177/1073858406287717. View