Graphene quantum dots induce apoptosis, autophagy, and inflammatory response via p38 mitogen-activated protein kinase and nuclear factor-κB mediated signaling pathways in activated THP-1 macrophages

Qin, Yiru; Zhou, Zhi Wei; Pan, Shu; He, Zijiang J.; Zhang, Xueji; Qiu, Jijun; Duan, Wei; Yang, Tianxin; Zhou, Shu Feng

doi:10.1016/j.tox.2014.10.011

Cited by 177 publications

(120 citation statements)

References 76 publications

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“…68,69 Similarly, nano-sized GO, pristine graphene, and graphene quantum dots caused time-and concentration-dependent decreases in the MMP. 70,71 Altogether, the data from our findings clearly indicate that GO-AgNPs could cause mitochondrial dysfunction through loss of MMP.…”

Section: Effect Of Go-agnps On Mitochondrial Dysfunctionsupporting

confidence: 61%

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: Effect Of Go-agnps On Mitochondrial Dysfunctionsupporting

confidence: 61%

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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“…These results correlated with previous reseach that found that baicalin induced autophagy accompanied by downregulation of the p-Akt (Ser473) level leading to increased Atg5, Atg7 and Atg12 and then the conversion of LC3I to LC3II and finally autophagy induction (42). Increased p-p38 leading to inhibition or induction of autophagy depends on the cellular context and cell type (43). Alisertib was reported to increase the p-p38 level correlated with highly accumulated LC3II in MCF-7 and MDA-MB-231 cells (44).…”

Section: Discussionsupporting

confidence: 91%

“…Alisertib was reported to increase the p-p38 level correlated with highly accumulated LC3II in MCF-7 and MDA-MB-231 cells (44). Furthermore, graphene quantum dots (GQDs) significantly increased p-p38 which was correlated with increased Beclin-1 and LC3II (43). In addition, increased p-JNK1/2 activation occurred upstream of the autophagy induction when cells were starved (45).…”

Section: Discussionmentioning

confidence: 99%

Goniothalamin induces apoptosis associated with autophagy activation through MAPK signaling in SK-BR-3 cells

2016

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Abstract. Goniothalamin, a plant bioactive styrly-lactone, possesses many biological activities. In the present study, the anticancer effect of goniothalamin on human breast cancer cell line SK-BR-3 was investigated. The results showed that goniothalamin induced nuclear condensation, DNA fragmentation, apoptotic bodies and mitochondrial dysfunction as determined by JC-1 staining. Goniothalamin also increased the Bax/Bcl-2 ratio and expression of cleaved caspase-7, cleaved caspase-9 and cleaved PARP, but decreased Bcl-2 expression. In addition, goniothalamin induced apoptosis via p-JNK1/2 and p-p38 upregulation and inhibited cell survival via p-ERK1/2 and p-Akt downregulation. Notably, goniothalamin induced autophagy through upregulation of Atg7, Atg12-Atg5 conjugation and LC3II. The increased p-p38 and p-JNK1/2 and decreased p-Akt may lead to autophagy induction. Therefore, goniothalamin promoted apoptosis associated with autophagy induction in SK-BR-3 cells through p-p38 and p-JNK1/2 upregulation and p-Akt downregulation. The present study indicated that goniothalamin may be further used as a potential therapeutic candidate or may offer an alternative treatment for breast cancer.

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“…23,24 In particular, apoptosis, autophagy, and necroptosis are usually involved in GBMs toxicology. [25][26][27] Many studies have reported that the different physicochemical properties of GBMs result in various cellular toxicities, and GBMs induce cell death in dose-or time-dependent manner. 28 However, the detailed mechanism of PCD induced by GBMs has not been well elucidated.…”

Section: Introductionmentioning

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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Graphene quantum dots induce apoptosis, autophagy, and inflammatory response via p38 mitogen-activated protein kinase and nuclear factor-κB mediated signaling pathways in activated THP-1 macrophages

Cited by 177 publications

References 76 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

Goniothalamin induces apoptosis associated with autophagy activation through MAPK signaling in SK-BR-3 cells

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

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Graphene quantum dots induce apoptosis, autophagy, and inflammatory response via p38 mitogen-activated protein kinase and nuclear factor-κB mediated signaling pathways in activated THP-1 macrophages

Cited by 177 publications

References 76 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

Goniothalamin induces apoptosis associated with autophagy activation through MAPK signaling in SK-BR-3 cells

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