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Int J Mol Sci. 2018 Dec 7;19(12). pii: E3939. doi: 10.3390/ijms19123939.

Effects of Reduced Graphene Oxides on Apoptosis and Cell Cycle of Glioblastoma Multiforme.

Author information

1
Department of Animal Nutrition and Biotechnology, Faculty of Animal Sciences, Warsaw University of Life Sciences, 02-787 Warsaw, Poland. jaroslaw_szczepaniak@sggw.pl.
2
Department of Animal Nutrition and Biotechnology, Faculty of Animal Sciences, Warsaw University of Life Sciences, 02-787 Warsaw, Poland. barbara_strojny@sggw.pl.
3
Department of Animal Nutrition and Biotechnology, Faculty of Animal Sciences, Warsaw University of Life Sciences, 02-787 Warsaw, Poland. ewa_sawosz@sggw.pl.
4
Department of Animal Nutrition and Biotechnology, Faculty of Animal Sciences, Warsaw University of Life Sciences, 02-787 Warsaw, Poland. slawomir_jaworski@sggw.pl.
5
Department of Chemical Synthesis and Flake Graphene, Institute of Electronic Materials Technology, 01-919 Warsaw, Poland. joanna_jagiello@itme.edu.pl.
6
Department of Chemical Synthesis and Flake Graphene, Institute of Electronic Materials Technology, 01-919 Warsaw, Poland. magdalena.winkowska@itme.edu.pl.
7
Department of Morphologic Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland. Maciej.Szmidt@Acurian.com.
8
Department of Animal Nutrition and Biotechnology, Faculty of Animal Sciences, Warsaw University of Life Sciences, 02-787 Warsaw, Poland. mateusz_wierzbicki@sggw.pl.
9
Department of Animal Nutrition and Biotechnology, Faculty of Animal Sciences, Warsaw University of Life Sciences, 02-787 Warsaw, Poland. malwina_sosnowska@sggw.pl.
10
Department of Animal Nutrition and Biotechnology, Faculty of Animal Sciences, Warsaw University of Life Sciences, 02-787 Warsaw, Poland. jasmina_balaban@sggw.pl.
11
Department of Pathology and Veterinary Diagnostics, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland. anna_winnicka@sggw.pl.
12
Department of Chemical Synthesis and Flake Graphene, Institute of Electronic Materials Technology, 01-919 Warsaw, Poland. ludwika_lipinska@itme.edu.pl.
13
Department of Pathology and Veterinary Diagnostics, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland. olga_witkowska_pilaszewicz@sggw.pl.
14
Department of Animal Nutrition and Biotechnology, Faculty of Animal Sciences, Warsaw University of Life Sciences, 02-787 Warsaw, Poland. marta_grodzik@sggw.pl.

Abstract

Graphene (GN) and its derivatives (rGOs) show anticancer properties in glioblastoma multiforme (GBM) cells in vitro and in tumors in vivo. We compared the anti-tumor effects of rGOs with different oxygen contents with those of GN, and determined the characteristics of rGOs useful in anti-glioblastoma therapy using the U87 glioblastoma line. GN/ExF, rGO/Term, rGO/ATS, and rGO/TUD were structurally analysed via transmission electron microscopy, Raman spectroscopy, FTIR, and AFM. Zeta potential, oxygen content, and electrical resistance were determined. We analyzed the viability, metabolic activity, apoptosis, mitochondrial membrane potential, and cell cycle. Caspase- and mitochondrial-dependent apoptotic pathways were investigated by analyzing gene expression. rGO/TUD induced the greatest decrease in the metabolic activity of U87 cells. rGO/Term induced the highest level of apoptosis compared with that induced by GN/ExF. rGO/ATS induced a greater decrease in mitochondrial membrane potential than GN/ExF. No significant changes were observed in the cytometric study of the cell cycle. The effectiveness of these graphene derivatives was related to the presence of oxygen-containing functional groups and electron clouds. Their cytotoxicity mechanism may involve electron clouds, which are smaller in rGOs, decreasing their cytotoxic effect. Overall, cytotoxic activity involved depolarization of the mitochondrial membrane potential and the induction of apoptosis in U87 glioblastoma cells.

KEYWORDS:

JC-1; apoptosis; brain tumor; cell cycle; glioblastoma multiforme; reduced graphene oxide

PMID:
30544611
PMCID:
PMC6320889
DOI:
10.3390/ijms19123939
[Indexed for MEDLINE]
Free PMC Article

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