Effects of Cerium Oxide Nanoparticles on PC12 Neuronal-Like Cells: Proliferation, Differentiation, and Dopamine Secretion

Ciofani, Gianni; Genchi, Giada Graziana; Liakos, Ioannis; Cappello, Valentina; Gemmi, Mauro; Athanassiou, Athanassia; Mazzolai, Barbara; Mattoli, Virgilio

doi:10.1007/s11095-013-1071-y

Cited by 89 publications

(72 citation statements)

References 41 publications

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“…109 Interestingly, there are limited reports about the adverse effects of cerium oxide nanoparticle exposures; in fact, many reports report their cytoprotective and proliferative nature. 110−112 However, in the present investigation, a reduction in TK6 cell proliferation (Figure 3C) by 16% was observed after 4 h exposure of cerium ENPs.…”

Section: Resultscontrasting

confidence: 60%

High-Throughput Screening Platform for Engineered Nanoparticle-Mediated Genotoxicity Using CometChip Technology

Watson¹,

Cohen³

et al. 2014

ACS Nano

141

124

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The likelihood of intentional and unintentional engineered nanoparticle (ENP) exposure has dramatically increased due to the use of nanoenabled products. Indeed, ENPs have been incorporated in many useful products and have enhanced our way of life. However, there are many unanswered questions about the consequences of nanoparticle exposures, in particular, with regard to their potential to damage the genome and thus potentially promote cancer. In this study, we present a high-throughput screening assay based upon the recently developed CometChip technology, which enables evaluation of single-stranded DNA breaks, abasic sites, and alkali-sensitive sites in cells exposed to ENPs. The strategic microfabricated, 96-well design and automated processing improves efficiency, reduces processing time, and suppresses user bias in comparison to the standard comet assay. We evaluated the versatility of this assay by screening five industrially relevant ENP exposures (SiO2, ZnO, Fe2O3, Ag, and CeO2) on both suspension human lymphoblastoid (TK6) and adherent Chinese hamster ovary (H9T3) cell lines. MTT and CyQuant NF assays were employed to assess cellular viability and proliferation after ENP exposure. Exposure to ENPs at a dose range of 5, 10, and 20 μg/mL induced dose-dependent increases in DNA damage and cytotoxicity. Genotoxicity profiles of ZnO > Ag > Fe2O3 > CeO2 > SiO2 in TK6 cells at 4 h and Ag > Fe2O3 > ZnO > CeO2 > SiO2 in H9T3 cells at 24 h were observed. The presented CometChip platform enabled efficient and reliable measurement of ENP-mediated DNA damage, therefore demonstrating the efficacy of this powerful tool in nanogenotoxicity studies.

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Section: Resultscontrasting

confidence: 60%

High-Throughput Screening Platform for Engineered Nanoparticle-Mediated Genotoxicity Using CometChip Technology

Watson¹,

Cohen³

et al. 2014

ACS Nano

141

124

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“…5 Ceria nanoparticles (CNPs) have received considerable attention for their excellent catalytic capability derived from the rapid alteration of the oxidation state from Ce 3+ to Ce 4+ . 6 CNPs have emerged as important and lucrative materials in biological fields such as neuroprotection, radiotherapy, ocular protection, bioanalysis, biomedicine, and antioxidant therapy; 7 in vitro and in vivo experiments suggest that CNPs have antioxidant and anti-inflammatory functions [8][9][10] but can also induce lipid 4958 chen et al peroxidation, lung damage, reactive oxygen species (ROS) production, and autophagy. 11 Other groups have previously investigated the potential of CNPs to protect normal cells against radiation-induced damage.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells

Chen¹,

Zhang²,

Hu³

et al. 2015

IJN

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Radiotherapy is one of the main strategies for cancer treatment but has significant challenges, such as cancer cell resistance and radiation damage to normal tissue. Radiosensitizers that selectively increase the susceptibility of cancer cells to radiation can enhance the effectiveness of radiotherapy. We report here the development of a novel radiosensitizer consisting of monodispersed ceria nanoparticles (CNPs) covered with the anticancer drug neogambogic acid (NGA-CNPs). These were used in conjunction with radiation in MCF-7 breast cancer cells, and the efficacy and mechanisms of action of this combined treatment approach were evaluated. NGA-CNPs potentiated the toxic effects of radiation, leading to a higher rate of cell death than either treatment used alone and inducing the activation of autophagy and cell cycle arrest at the G2/M phase, while pretreatment with NGA or CNPs did not improve the rate of radiation-induced cancer cells death. However, NGA-CNPs decreased both endogenous and radiation-induced reactive oxygen species formation, unlike other nanomaterials. These results suggest that the adjunctive use of NGA-CNPs can increase the effectiveness of radiotherapy in breast cancer treatment by lowering the radiation doses required to kill cancer cells and thereby minimizing collateral damage to healthy adjacent tissue.

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“…The studies were carried out using rat pheochromocytoma (PC12) cells [24]–[26]. PC12 cells were a kind gift from Prof. Anne Eckert (Neurobiology Laboratory for Brain Aging and Mental Health University of Basel, Basel, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

Extracellular α-Synuclein Leads to Microtubule Destabilization via GSK-3β-Dependent Tau Phosphorylation in PC12 Cells

et al. 2014

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α-Synuclein (ASN) plays an important role in pathogenesis of Parkinson's disease (PD) and other neurodegenerative disorders. Novel and most interesting data showed elevated tauopathy in PD and suggested relationship between ASN and Tau protein. However, the mechanism of ASN-evoked Tau protein modification is not fully elucidated. In this study we investigated the role of extracellular ASN in Tau hyperphosphorylation in rat pheochromocytoma (PC12) cells and the involvement of glycogen synthase kinase-3β (GSK-3β) and cyclin-dependent kinase 5 (CDK5) in ASN-dependent Tau modification. Our results indicated that exogenously added ASN increases Tau phosphorylation at Ser396. Accordingly, the GSK-3β inhibitor (SB-216763) prevented ASN-evoked Tau hyperphosphorylation, but the CDK5 inhibitor had no effect. Moreover, western blot analysis showed that ASN affected GSK-3β via increasing of protein level and activation of this enzyme. GSK-3β activity evaluated by its phosphorylation status assay showed that ASN significantly increased the phosphorylation of this enzyme at Tyr216 with parallel decrease in phosphorylation at Ser9, indicative of stimulation of GSK-3β activity. Moreover, the effect of ASN on microtubule (MT) destabilization and cell death with simultaneous the involvement of GSK-3β in these processes were analyzed. ASN treatment increased the amount of free tubulin and concomitantly reduced the amount of polymerized tubulin and SB-216763 suppressed these ASN-induced changes in tubulin, indicating that GSK-3β is involved in ASN-evoked MT destabilization. ASN-induced apoptotic processes lead to decrease in PC12 cells viability and SB-216763 protected those cells against ASN-evoked cytotoxicity. Concluding, extracellular ASN is involved in GSK-3β-dependent Tau hyperphosphorylation, which leads to microtubule destabilization. GSK-3β inhibition may be an effective strategy for protecting against ASN-induced cytotoxicity.

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Effects of Cerium Oxide Nanoparticles on PC12 Neuronal-Like Cells: Proliferation, Differentiation, and Dopamine Secretion

Abstract: Even if deeper examinations will be necessary in order to better clarify the mechanisms at the base of the documented effects, nanoceria demonstrated a significant potential as pharmacological agent in the treatment of neurological disorders.

Cited by 89 publications

References 41 publications

High-Throughput Screening Platform for Engineered Nanoparticle-Mediated Genotoxicity Using CometChip Technology

High-Throughput Screening Platform for Engineered Nanoparticle-Mediated Genotoxicity Using CometChip Technology

Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells

Extracellular α-Synuclein Leads to Microtubule Destabilization via GSK-3β-Dependent Tau Phosphorylation in PC12 Cells

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Effects of Cerium Oxide Nanoparticles on PC12 Neuronal-Like Cells: Proliferation, Differentiation, and Dopamine Secretion

Abstract: Even if deeper examinations will be necessary in order to better clarify the mechanisms at the base of the documented effects, nanoceria demonstrated a significant potential as pharmacological agent in the treatment of neurological disorders.

Cited by 89 publications

References 41 publications

High-Throughput Screening Platform for Engineered Nanoparticle-Mediated Genotoxicity Using CometChip Technology

High-Throughput Screening Platform for Engineered Nanoparticle-Mediated Genotoxicity Using CometChip Technology

Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in&nbsp;breast cancer cells

Extracellular α-Synuclein Leads to Microtubule Destabilization via GSK-3β-Dependent Tau Phosphorylation in PC12 Cells

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Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells