Surface-modified magnetite nanoparticles act as aneugen-like spindle poison

Buliaková, Barbora; Mesárošová, Monika; Bábelová, Andrea; Selc, Michal; Némethová, Veronika; Sebová, Lívia; Rázga, Filip; Ursı́nyová, Monika; Chalupa, Ivan; Gábelová, Alena

doi:10.1016/j.nano.2016.08.027

Cited by 12 publications

(5 citation statements)

References 54 publications

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“…In the current study using BEAS-2B cells, Ni NPs showed some divergent effects compared to NiO NPs, such as an increased proliferation, in line with previous findings [ 22 ], effects similar to aneugen-like spindle poisons, and endoreduplications (duplication of nuclear genome in the absence of cell division). Interestingly, endoreduplications and multinuclear cells as well as disruption of tubulin filaments were recently reported in A549 lung carcinoma cells following exposure to magnetite NPs [ 49 ]. In general, interference with the cytoskeleton organization/tubulin filaments appears plausible in cells with high content of NPs [ 50 – 52 ].…”

Section: Discussionmentioning

confidence: 99%

Calcium-dependent cyto- and genotoxicity of nickel metal and nickel oxide nanoparticles in human lung cells

et al. 2018

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BackgroundGenotoxicity is an important toxicological endpoint due to the link to diseases such as cancer. Therefore, an increased understanding regarding genotoxicity and underlying mechanisms is needed for assessing the risk with exposure to nanoparticles (NPs). The aim of this study was to perform an in-depth investigation regarding the genotoxicity of well-characterized Ni and NiO NPs in human bronchial epithelial BEAS-2B cells and to discern possible mechanisms. Comparisons were made with NiCl2 in order to elucidate effects of ionic Ni.MethodsBEAS-2B cells were exposed to Ni and NiO NPs, as well as NiCl2, and uptake and cellular dose were investigated by transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS). The NPs were characterized in terms of surface composition (X-ray photoelectron spectroscopy), agglomeration (photon cross correlation spectroscopy) and nickel release in cell medium (ICP-MS). Cell death (necrosis/apoptosis) was investigated by Annexin V-FITC/PI staining and genotoxicity by cytokinesis-block micronucleus (cytome) assay (OECD 487), chromosomal aberration (OECD 473) and comet assay. The involvement of intracellular reactive oxygen species (ROS) and calcium was explored using the fluorescent probes, DCFH-DA and Fluo-4.ResultsNPs were efficiently taken up by the BEAS-2B cells. In contrast, no or minor uptake was observed for ionic Ni from NiCl2. Despite differences in uptake, all exposures (NiO, Ni NPs and NiCl2) caused chromosomal damage. Furthermore, NiO NPs were most potent in causing DNA strand breaks and generating intracellular ROS. An increase in intracellular calcium was observed and modulation of intracellular calcium by using inhibitors and chelators clearly prevented the chromosomal damage. Chelation of iron also protected against induced damage, particularly for NiO and NiCl2.ConclusionsThis study has revealed chromosomal damage by Ni and NiO NPs as well as Ni ionic species and provides novel evidence for a calcium-dependent mechanism of cyto- and genotoxicity.Electronic supplementary materialThe online version of this article (10.1186/s12989-018-0268-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Calcium-dependent cyto- and genotoxicity of nickel metal and nickel oxide nanoparticles in human lung cells

et al. 2018

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“…Western blot analysis was performed as described previously [ 30 ]. ALDH1–specific antibody (BD Biosciences cat.…”

Section: Methodsmentioning

confidence: 99%

ALDH1A inhibition sensitizes colon cancer cells to chemotherapy

et al. 2018

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BackgroundRecent evidence in cancer research, developed the notion that malignant tumors consist of different subpopulations of cells, one of them, known as cancer stem cells, being attributed many important properties such as enhanced tumorigenicity, proliferation potential and profound multidrug resistance to chemotherapy. Several key stem cells markers were identified in colon cancer. In our study we focused on the aldehyde dehydrogenase type 1 (ALDH1) expression in colon cancer-derived cell lines HT-29/eGFP, HCT-116/eGFP and LS-180/eGFP, and its role in the chemoresistance and tumorigenic potential.MethodsThe effect of pharmacological inhibition of ALDH activity by diethylaminobenzaldehyde (DEAB) and also effect of molecular inhibition by specific siRNA was evaluated in vitro in cultures of human colorectal cell lines. The expression level of different isoenzymes of aldehyde dehydrogenase was determined using qPCR. Changes in cell biology were evaluated by expression analysis, western blot and apoptosis assay. The efficiency of cytotoxic treatment in the presence of different chemotherapeutic drugs was analyzed by fluorimetric assay. Tumorigenicity of cells with specific ALDH1A1 siRNA was tested in xenograft model in vivo.ResultsTreatment by DEAB partially sensitized the tested cell lines to chemotherapeutics. Subsequently the molecular inhibition of specific isoforms of ALDH by ALDH1A1 or ALDH1A3 siRNA led to sensitizing of cell lines HT-29/eGFP, HCT-116/eGFP to capecitabine and 5-FU. On the model of athymic mice we observed the effect of molecular inhibition of ALDH1A1 in HT-29/eGFP cells by siRNA. We observed inhibition of proliferation of subcutaneous xenografts in comparison to control cells.ConclusionThis research, verifies the significance of the ALDH1A isoforms in multidrug resistance of human colorectal cancer cells and its potential as a cancer stem cell marker. This provides the basis for the development of new approaches regarding the treatment of patients with colorectal adenocarcinoma and potentially the treatment of other tumor malignancies.

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“…Noc affects microtubule formation, thus interfering with cytoskeleton structure and mitosis, leading to cell cycle arrest in G2/M [ 26 ]. As MNPs interfere with tubulin polymerization as well [ 27 ], the combined treatment could multiply the microtubule-disrupting effect of Noc.…”

Section: Resultsmentioning

confidence: 99%

Differences in surface chemistry of iron oxide nanoparticles result in different routes of internalization

Svitkova¹,

Závišová²,

Némethová³

et al. 2021

Beilstein J. Nanotechnol.

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The efficient entry of nanotechnology-based pharmaceuticals into target cells is highly desired to reach high therapeutic efficiency while minimizing the side effects. Despite intensive research, the impact of the surface coating on the mechanism of nanoparticle uptake is not sufficiently understood yet. Herein, we present a mechanistic study of cellular internalization pathways of two magnetic iron oxide nanoparticles (MNPs) differing in surface chemistry into A549 cells. The MNP uptake was investigated in the presence of different inhibitors of endocytosis and monitored by spectroscopic and imaging techniques. The results revealed that the route of MNP entry into cells strongly depends on the surface chemistry of the MNPs. While serum bovine albumin-coated MNPs entered the cells via clathrin-mediated endocytosis (CME), caveolin-mediated endocytosis (CavME) or lipid rafts were preferentially involved in the internalization of polyethylene glycol-coated MNPs. Our data indicate that surface engineering can contribute to an enhanced delivery efficiency of nanoparticles.

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Surface-modified magnetite nanoparticles act as aneugen-like spindle poison

Cited by 12 publications

References 54 publications

Calcium-dependent cyto- and genotoxicity of nickel metal and nickel oxide nanoparticles in human lung cells

Calcium-dependent cyto- and genotoxicity of nickel metal and nickel oxide nanoparticles in human lung cells

ALDH1A inhibition sensitizes colon cancer cells to chemotherapy

Differences in surface chemistry of iron oxide nanoparticles result in different routes of internalization

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