Oxidative Stress and Mitochondrial Activation as the Main Mechanisms Underlying Graphene Toxicity against Human Cancer Cells

Jarosz, Anna; Skoda, Marta; Dudek, Ilona; Szukiewicz, Dariusz

doi:10.1155/2016/5851035

Cited by 97 publications

(82 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For instance, rGO bonded to cell membranes, stimulated receptors and activated mitochondrial pathways, inducing apoptosis [110, 111, 144]. Limited evidence showed that GO is smaller and less toxic than rGO because of the high oxygen content, smoother edges, and hydrophilic properties of the former species [104, 145, 146]. Because of the different surface oxidation states of GO and rGO, GO possessing distinct hydrophilicity might be internalized and taken up by HepG2 cells easily.…”

Section: Origins Of Gfns Toxicitymentioning

confidence: 99%

Toxicity of graphene-family nanoparticles: a general review of the origins and mechanisms

et al. 2016

View full text Add to dashboard Cite

Due to their unique physicochemical properties, graphene-family nanomaterials (GFNs) are widely used in many fields, especially in biomedical applications. Currently, many studies have investigated the biocompatibility and toxicity of GFNs in vivo and in intro. Generally, GFNs may exert different degrees of toxicity in animals or cell models by following with different administration routes and penetrating through physiological barriers, subsequently being distributed in tissues or located in cells, eventually being excreted out of the bodies. This review collects studies on the toxic effects of GFNs in several organs and cell models. We also point out that various factors determine the toxicity of GFNs including the lateral size, surface structure, functionalization, charge, impurities, aggregations, and corona effect ect. In addition, several typical mechanisms underlying GFN toxicity have been revealed, for instance, physical destruction, oxidative stress, DNA damage, inflammatory response, apoptosis, autophagy, and necrosis. In these mechanisms, (toll-like receptors-) TLR-, transforming growth factor β- (TGF-β-) and tumor necrosis factor-alpha (TNF-α) dependent-pathways are involved in the signalling pathway network, and oxidative stress plays a crucial role in these pathways. In this review, we summarize the available information on regulating factors and the mechanisms of GFNs toxicity, and propose some challenges and suggestions for further investigations of GFNs, with the aim of completing the toxicology mechanisms, and providing suggestions to improve the biological safety of GFNs and facilitate their wide application.

show abstract

Section: Origins Of Gfns Toxicitymentioning

confidence: 99%

Toxicity of graphene-family nanoparticles: a general review of the origins and mechanisms

et al. 2016

View full text Add to dashboard Cite

show abstract

“…28 However, the detailed mechanism of PCD induced by GBMs has not been well elucidated. Since many other reviews had illustrated that the different physicochemical properties of GBMs largely impacted on the cell toxicity, [29][30][31] we concentrate on summarizing the pathways of PCD induced by GBMs in this review, and leave aside the effect of administration route, administration dose, and the physicochemical properties of GBMs.…”

Section: Introductionmentioning

confidence: 99%

“…The generation of ROS is considered the primary cause of cell death. 31,34 The increased ROS generation leads to apoptosis and autophagy with an increase in the expression levels of apoptotic and autophagic effectors, such as caspase-3, caspase-9, Beclin-1, Bax, Bad, and LC3-I/II, after exposure to GBMs. 26,27 ROS induces the loss of the mitochondrial membrane that potentially initiates both apoptosis and necrosis.…”

mentioning

confidence: 99%

The mechanisms of graphene-based materials-induced programmed cell death: a review of apoptosis, autophagy, and programmed necrosis

Lin

Song

et al. 2017

IJN

159

108

View full text Add to dashboard Cite

Graphene-based materials (GBMs) are widely used in many fields, including biomedicine. To date, much attention had been paid to the potential unexpected toxic effects of GBMs. Here, we review the recent literature regarding the impact of GBMs on programmed cell death (PCD). Apoptosis, autophagy, and programmed necrosis are three major PCDs. Mechanistic studies demonstrated that the mitochondrial pathways and MAPKs (JNK, ERK, and p38)- and TGF-β-related signaling pathways are implicated in GBMs-induced apoptosis. Autophagy, unlike apoptosis and necroptosis which are already clear cell death types, plays a vital pro-survival role in cell homeostasis, so its role in cell death should be carefully considered. However, GBMs always induce unrestrained autophagy accelerating cell death. GBMs trigger autophagy through inducing autophagosome accumulation and lysosome impairment. Mitochondrial dysfunction, ER stress, TLRs signaling pathways, and p38 MAPK and NF-κB pathways participate in GBMs-induced autophagy. Programmed necrosis can be activated by RIP kinases, PARP, and TLR-4 signaling in macrophages after GBMs exposure. Though apoptosis, autophagy, and necroptosis are distinguished by some characteristics, their numerous signaling pathways comprise an interconnected network and correlate with each other, such as the TLRs, p53 signaling pathways, and the Beclin-1 and Bcl-2 interaction. A better understanding of the mechanisms of PCD induced by GBMs may allow for a thorough study of the toxicology of GBMs and a more precise determination of the consequences of human exposure to GBMs. These determinations will also benefit safety assessments of the biomedical and therapeutic applications of GBMs.

show abstract

“…25 Oxidative stress and generation of ROS can be involved in the toxic effects of graphene-based nanomaterials. 26 Assessment of ROS production showed a toxic influence of HNC on glioma cells.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the cytotoxicity of hierarchical nanoporous graphenic carbon against human glioblastoma grade IV cells

Jaworski

Biniecka

Bugajska

et al. 2017

IJN

View full text Add to dashboard Cite

A newly produced hierarchical, nanoporous carbon (HNC) material is studied for the first time in a biological model. The material consists of uniform particles and is characterized by a mean diameter <150 nm, a high specific surface area of 1,000 m 2 /g, well-developed porosity, and high electrical conductivity. These unique properties and ability to transfer charge create a possibility of employing HNC as a moderator of tumor cell growth. As the charge of HNC may interfere with cell membranes by adhesion and by bonding with cell receptors, it may block the supply of nutrients. The interactions of HNC with the U87 cells can also lead to the excessive generation of reactive oxygen species (ROS) and activate apoptotic mechanisms in cancer cells. The investigation was performed using U87 human glioblastoma and PCS-201–010 normal fibroblast cell lines, where cell morphology and ultrastructure, viability, ROS production, type of cell death, mitochondrial transmembrane potential, and the expression of genes engaged in apoptosis pathways are studied. The results demonstrate that cytotoxicity of HNC particles increases with concentration from 5 to 100 µg/mL by activation of apoptosis through the mitochondrial pathway, without inducing necrosis. Our research indicates the potential applicability of HNC in cancer therapy.

show abstract

Oxidative Stress and Mitochondrial Activation as the Main Mechanisms Underlying Graphene Toxicity against Human Cancer Cells

Cited by 97 publications

References 62 publications

Toxicity of graphene-family nanoparticles: a general review of the origins and mechanisms

Toxicity of graphene-family nanoparticles: a general review of the origins and mechanisms

The mechanisms of graphene-based materials-induced programmed cell death: a review of apoptosis, autophagy, and programmed necrosis

Analysis of the cytotoxicity of hierarchical nanoporous graphenic carbon against human glioblastoma grade IV cells

Contact Info

Product

Resources

About