Gold nanoparticles induce nuclear damage in breast cancer cells, which is further amplified by hyperthermia

Kodiha, Mohamed; Hutter, Eliza; Boridy, Sebastien; Juhas, Michal; Maysinger, Dušica; Stochaj, Ursula

doi:10.1007/s00018-014-1622-3

Cited by 59 publications

(53 citation statements)

References 54 publications

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“…the spatial separation of FC, DFC and GC . Such reorganization is accompanied by a redistribution of nucleolar proteins and changes in nucleolar activities . Some stressors go beyond these effects, as they induce the formation of the nucleolar aggresome, a stress‐induced nucleolar subcompartment with unique molecular make‐up .…”

Section: The Nucleolus Functions As a Ribosome Factory And Stress Sensormentioning

confidence: 99%

Nucleoli and Stress Granules: Connecting Distant Relatives

Mahboubi

Stochaj

2014

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Nucleoli and cytoplasmic stress granules (SGs) are subcellular compartments that modulate the response to endogenous and environmental signals to control cell survival. In our opinion, nucleoli and SGs are functionally linked; they are distant relatives that combine forces when cellular homeostasis is threatened. Several lines of evidence support this idea; nucleoli and SGs share molecular building blocks, are regulated by common signaling pathways and communicate when vital cellular functions become compromised. Together, nucleoli and SGs orchestrate physiological responses that are directly relevant to stress and human health.As both compartments have established roles in neurodegenerative diseases, cancer and virus infections, we propose that these conditions will benefit from therapeutic interventions that target simultaneously nucleoli and SGs.

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Section: The Nucleolus Functions As a Ribosome Factory And Stress Sensormentioning

confidence: 99%

Nucleoli and Stress Granules: Connecting Distant Relatives

Mahboubi

Stochaj

2014

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“…13 Previous research showed that nuclear membranes, nuclear laminae, and nucleolar functions were compromised by small spherical Au NPs or gold nanoflowers in breast cancer cells. 67 Dam et al reported that nanoconstructs composed of nucleolin-specific aptamers and gold nanostars were transferred to the perinuclear region and induced major changes to the nuclear phenotype via nuclear envelope invaginations. 68 Therefore, the nucleus might be mechanically disturbed by ZnO NP aggregates located in the perinucleus or by the ROS induced by these aggregates.…”

Section: Discussionmentioning

confidence: 99%

Zinc oxide nanoparticles-induced epigenetic change and G2/M arrest are associated with apoptosis in human epidermal keratinocytes

Gao

Zhou

et al. 2016

IJN

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As an engineered nanomaterial, zinc oxide nanoparticles (ZnO NPs) are used frequently in biological applications and can make contact with human skin. Here, we systematically investigated the effects of ZnO NPs on non-tumorigenic human epidermal keratinocytes, which were used as a test model for this in vitro study, at the epigenetic and molecular levels. Our results showed that ZnO NPs induced cell cycle arrest at the G2/M checkpoint before the viability of human epidermal keratinocytes was reduced, which was associated with the chromatin changes at the epigenetic level, including increased methylation of histone H3K9 and decreased acetylation of histone H4K5 accompanied by chromatin condensation at 24 hours. The mRNA expression of the methyltransferase genes G9a and GLP was also increased upon treatment with ZnO NPs, and the acetyltransferase genes GCN5 , P300 , and CBP were downregulated. Reactive oxygen species were found to be more abundant after treatment with ZnO NPs for 6 hours, and DNA damage was observed at 24 hours. Transmission electron microscopy and flow cytometry confirmed that ZnO NPs were absorbed into the cell when they were added to the medium. Apoptotic human epidermal keratinocytes were detected, and the expression of the proapoptotic genes Bax , Noxa , and Puma increased significantly, while the expression of the antiapoptotic gene Bcl-xl decreased 24 hours after exposure to ZnO NPs. These findings suggest that the ZnO NPs induced cell cycle arrest at G2/M, which was associated with epigenetic changes and accompanied by p53-Bax mitochondrial pathway-mediated apoptosis.

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“…Secondary antibodies were further purified by pre-adsorption to immobilized proteins prepared from mammalian culture cells [14]. [15,16]. 24 hours prior to the experiment, trypsinize cells and culture overnight on glass cover slips coated with poly-L-lysine.…”

Section: Reagentsmentioning

confidence: 99%

Detecting changes in the mitochondrial membrane potential by quantitative fluorescence microscopy

Stochaj¹,

Kodiha²,

Pié³

et al. 2015

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Mitochondria are the major energy providers in most mammalian cells. Mitochondrial dysfunction has been linked to multiple diseases and pathophysiologies, including a growing number of neurodegenerative disorders. Moreover, as key regulators of cell death, mitochondria are also prime targets for cancer research and at the center of drug development. The mitochondrial membrane potential is essential for ATP production and an important parameter to assess the functional state of these organelles. As MitoTracker® dyes concentrate in active mitochondria, they are ideal tools to evaluate mitochondrial function. We have developed a simple, fast and reliable protocol that measures MitoTracker® signals associated with mitochondria. Our protocol was successfully applied to assess changes in the mitochondrial membrane potential in diverse cell types from different organisms. The method developed by us provides a powerful tool for mitochondrial research and can be easily adapted for drug screening.

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Gold nanoparticles induce nuclear damage in breast cancer cells, which is further amplified by hyperthermia

Cited by 59 publications

References 54 publications

Nucleoli and Stress Granules: Connecting Distant Relatives

Nucleoli and Stress Granules: Connecting Distant Relatives

Zinc oxide nanoparticles-induced epigenetic change and G2/M arrest are associated with apoptosis in human epidermal keratinocytes

Detecting changes in the mitochondrial membrane potential by quantitative fluorescence microscopy

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