The triggering of apoptosis in macrophages by pristine graphene through the MAPK and TGF-beta signaling pathways

Yang, Li; Liu, Ying; Fu, Yujian; Wei, Taotao; Guyader, Laurent Le; Gao, Ge; Liu, Ru‐Shi; Chang, Yan-Zhong; Chen, Chunying

doi:10.1016/j.biomaterials.2011.09.091

Cited by 460 publications

(366 citation statements)

References 67 publications

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“…Several studies supported that the mechanism of ROS generation is due to the loss of mitochondrial function by graphene toxicity. Li et al 76 reported that pristine graphene caused a decrease in the MMP and, consequently, increased levels of intracellular ROS, which activate the mitochondria-dependent apoptotic pathway. On the other hand, GO-AgNPs could target the impairment of ATP production and the overproduction of ROS by decreasing the membrane potential of mitochondria.…”

Section: Go-agnps Enhance the Generation Of Ros In Sh-sy5y Cellsmentioning

confidence: 99%

Quercetin-mediated synthesis of graphene oxide–silver nanoparticle nanocomposites: a suitable alternative nanotherapy for neuroblastoma

Yuan¹,

Wang²,

Xing³

et al. 2017

IJN

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Background Graphene and graphene-related materials have gained substantial interest from both academia and industry for the development of unique nanomaterials for biomedical applications. Graphene oxide (GO) and silver nanoparticles (AgNPs) are a valuable platform for the development of nanocomposites, permitting the combination of nanomaterials with different physical and chemical properties to generate novel materials with improved and effective functionalities in a single platform. Therefore, this study was conducted to synthesize a graphene oxide–silver nanoparticle (GO-AgNPs) nanocomposite using the biomolecule quercetin and evaluate the potential cytotoxicity and mechanism of GO-AgNPs in human neuroblastoma cancer cells (SH-SY5Y). Methods The synthesized GO-AgNPs were characterized using various analytical techniques. The potential toxicities of GO-AgNPs were evaluated using a series of biochemical and cellular assays. The expression of apoptotic and anti-apoptotic genes was measured by quantitative real-time reverse transcription polymerase chain reaction. Further, apoptosis was confirmed by caspase-9/3 activity and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and GO-AgNPs-induced autophagy was also confirmed by transmission electron microscopy. Results The prepared GO-AgNPs exhibited significantly higher cytotoxicity toward SH-SY5Y cells than GO. GO-AgNPs induced significant cytotoxicity in SH-SY5Y cells by the loss of cell viability, inhibition of cell proliferation, increased leakage of lactate dehydrogenase, decreased level of mitochondrial membrane potential, reduced numbers of mitochondria, enhanced level of reactive oxygen species generation, increased expression of pro-apoptotic genes, and decreased expression of anti-apoptotic genes. GO-AgNPs induced caspase-9/3-dependent apoptosis via DNA fragmentation. Finally, GO-AgNPs induced accumulation of autophagosomes and autophagic vacuoles. Conclusion In this study, we developed an environmentally friendly, facile, dependable, and simple method for the synthesis of GO-AgNPs nanocomposites using quercetin. The synthesized GO-AgNPs exhibited enhanced cytotoxicity compared with that of GO at very low concentrations. This study not only elucidates the potential cytotoxicity against neuroblastoma cancer cells, but also reveals the molecular mechanism of toxicity.

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Section: Go-agnps Enhance the Generation Of Ros In Sh-sy5y Cellsmentioning

confidence: 99%

Quercetin-mediated synthesis of graphene oxide–silver nanoparticle nanocomposites: a suitable alternative nanotherapy for neuroblastoma

Yuan¹,

Wang²,

Xing³

et al. 2017

IJN

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“…[ 67 ] Although the mechanisms for their toxicity toward cells are not completely understood as they follow different paths, [ 68 ] the formation of reactive oxygen species seems to be the most recurring mechanism observed. [ 69,70 ] While pristine carbon based materials tend to accumulate in physiological solution due to electrostatic interactions and nonspecifi c bindings to proteins, [ 71 ] surface-modifi ed graphene-like materials are often deemed to be less toxic. [ 70,72 ] Our results are consistent with these observations.…”

Section: Advmentioning

confidence: 99%

Thermally Reduced Graphene Oxide Nanohybrids of Chiral Functional Naphthalenediimides for Prostate Cancer Cells Bioimaging

Tyson

Mirabello

Calatayud

et al. 2016

Adv Funct Materials

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This study reports on the supramolecular assemblies formed between planar carbon systems (PCSs) such as thermally reduced graphene oxide (TRGO) and its small‐molecule model system coronene and a series of d‐ and l‐α amino acid derivatized naphthalenediimides (NDIs) where the halogen substituents (X = F, Cl, Br, I) are varied systematically. Confocal fluorescence microscopy of NDIs, NDI•coronene, and NDI•TRGO complexes is performed proving the uptake and stability of such complexes in the cellular environment and suggesting their potential as prostate cancer imaging agents. 1H NMR and UV–vis spectroscopy studies support the formation of charge transfer complexes whereby the increasing polarizability and general electronegativity of the aryl halide substituted at the NDI periphery influence the magnitude of the association constants in the ground state between NDI and coronene. Complexation between NDIs and PCSs also results in stable photoexcited assemblies within the solution (coronene) as well as the dispersed phased (TRGO). Fluorescence emission titrations and 2‐photon time correlated single photon counting measurements suggest the existence of dynamic quenching mechanisms upon the excitation of the fluorophore in the presence of the carbon substrates, as these methods are sensitive proves for the subtle changes in the NDI environment. The series of halogenated species used exerts supramolecular control over the degree of surface assembly on the TRGO and over the interactions with the coronene molecule, and this is of relevance to the assembly of future biosensing platforms as these materials can both be viewed as congeners of graphene. Finally, MTT assays carried out in PC‐3 cells demonstrate that the stable noncovalent functionalization of TRGO and coronene with either l or d NDIs remarkably improves the cellular viability in the presence of such graphene‐like materials. These phenomena are of particular relevance for the understanding of the direct donor–acceptor interactions in solutions which govern the design of nanomaterials with future biosensing and bioimaging applications.

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“…59,60 For example, caspase-3, one of the most important executioner caspases, and PARP are activated by mitochondrial pathways that initiate pristine graphenemediated apoptosis. 61,62 Exposure to graphene increases intracellular ROS generation, including mitochondria-produced …”

mentioning

confidence: 99%

“…62,63 Disruptions of the MMP may lead to broken electron transfer chain, decline in ATP synthesis, and release of proapoptotic molecules from the mitochondria to cytoplasm. Similarly, GO and rGO treatments also cause mitochondrial damage and accelerate apoptosis by generating oxidative stress.…”

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

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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.

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The triggering of apoptosis in macrophages by pristine graphene through the MAPK and TGF-beta signaling pathways

Cited by 460 publications

References 67 publications

Quercetin-mediated synthesis of graphene oxide–silver nanoparticle nanocomposites: a suitable alternative nanotherapy for neuroblastoma

Quercetin-mediated synthesis of graphene oxide–silver nanoparticle nanocomposites: a suitable alternative nanotherapy for neuroblastoma

Thermally Reduced Graphene Oxide Nanohybrids of Chiral Functional Naphthalenediimides for Prostate Cancer Cells Bioimaging

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

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The triggering of apoptosis in macrophages by pristine graphene through the MAPK and TGF-beta signaling pathways

Cited by 460 publications

References 67 publications

Quercetin-mediated synthesis of graphene oxide&ndash;silver nanoparticle nanocomposites: a suitable alternative nanotherapy for neuroblastoma

Quercetin-mediated synthesis of graphene oxide&ndash;silver nanoparticle nanocomposites: a suitable alternative nanotherapy for neuroblastoma

Thermally Reduced Graphene Oxide Nanohybrids of Chiral Functional Naphthalenediimides for Prostate Cancer Cells Bioimaging

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

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Quercetin-mediated synthesis of graphene oxide–silver nanoparticle nanocomposites: a suitable alternative nanotherapy for neuroblastoma

Quercetin-mediated synthesis of graphene oxide–silver nanoparticle nanocomposites: a suitable alternative nanotherapy for neuroblastoma