In vitro and bioinformatics mechanistic-based approach for cadmium carcinogenicity understanding

Oldani, Monica; Fabbri, Marco; Melchioretto, Pasquale; Callegaro, Giulia; Fusi, Paola; Gribaldo, Laura; Forcella, Matilde; Urani, Chiara

doi:10.1016/j.tiv.2020.104757

Cited by 10 publications

(11 citation statements)

References 79 publications

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“…Moreover, the CTA has been shown to closely model some key stages of the in vivo carcinogenic process [ 9 ]. In addition to be widely used for the screening of potential carcinogens [ 10 , 11 ], the CTA is also a powerful tool for mechanistic studies of carcinogenesis [ 12 , 13 ]. In our experiments, the CTA based on the use of C3H10T1/2Cl8 mouse embryo fibroblasts was adopted, the latter being among the suitable cells suggested by standard protocols [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…In particular, F1 focus showed ERK activation and a high proliferation rate, while F3 focus showed Akt activation and a survival molecular profile. More recently [ 12 ], a toxicogenomic study performed by our group, showed that, upon cadmium administration, the two foci also developed distinct patterns of up-regulated and down-regulated genes.…”

Section: Introductionmentioning

confidence: 99%

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Insights into Cadmium-Induced Carcinogenesis through an In Vitro Study Using C3H10T1/2Cl8 Cells: The Multifaceted Role of Mitochondria

Oldani

Villa

Manzoni

et al. 2021

IJMS

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In this paper, we report the metabolic characterization of two foci, F1 and F3, obtained at the end of Cell Transformation Assay (CTA), performed by treating C3H10T1/2Cl8 mouse embryo fibroblasts with 1 μM CdCl2 for 24 h. The elucidation of the cadmium action mechanism can be useful both to improve the in vitro CTA and to yield insights into carcinogenesis. The metabolism of the two foci was investigated through Seahorse and enzyme activity assays; mitochondria were studied in confocal microscopy and reactive oxygen species were detected by flow cytometry. The results showed that F1 focus has higher glycolytic and TCA fluxes compared to F3 focus, and a more negative mitochondrial membrane potential, so that most ATP synthesis is performed through oxidative phosphorylation. Confocal microscopy showed mitochondria crowded in the perinuclear region. On the other hand, F3 focus showed lower metabolic rates, with ATP mainly produced by glycolysis and damaged mitochondria. Overall, our results showed that cadmium treatment induced lasting metabolic alterations in both foci. Triggered by the loss of the Pasteur effect in F1 focus and by mitochondrial impairment in F3 focus, these alterations lead to a loss of coordination among glycolysis, TCA and oxidative phosphorylation, which leads to malignant transformation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Insights into Cadmium-Induced Carcinogenesis through an In Vitro Study Using C3H10T1/2Cl8 Cells: The Multifaceted Role of Mitochondria

Oldani

Villa

Manzoni

et al. 2021

IJMS

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“…Inflammation mediated by heavy metals (including cadmium) is associated with cancers (Oldani et al 2020) and neurodegenerative diseases such as AD (Huat et al 2019). Epidemiological studies indicate the association between cadmium exposure and brain cancers (Wesseling et al 2002;Rodrigues et al 2020).…”

Section: Introductionmentioning

confidence: 99%

“…In vitro studies have shown that cadmium was able to accumulate in human glioblastoma U-87 MG cells in a concentration-dependent manner and induced the production of interleukin (IL)-6 and IL-8 by activating ERK1/2, p38 mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-jB pathways (Phuagkhaopong et al 2017). Whole genome microarray analysis of differentiallyexpressed genes of cadmium-transformed fibroblasts showed the up-regulation of CCL2, CCL5, IL-6, and Secreted Phosphoprotein 1 (Spp1) mRNA (Oldani et al 2020). Lastly, it has also been reported that cadmium induced CCL2 expression and secretion in white adipose tissues and urine, respectively, in hosts exposed by subcutaneous injection and oral administration, respectively (Kawakami et al 2013;Lee et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Cadmium induces CCL2 production in glioblastoma cells via activation of MAPK, PI3K, and PKC pathways

Kasemsuk

Phuagkhaopong

Yubolphan

et al. 2020

Journal of Immunotoxicology

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Cadmium (Cd) is accumulated in human astrocytes and induces the production of interleukin (IL)-6 and IL-8. Astrocytes are one of the major sources of chemokine CC motif ligand 2 (CCL2; known as monocyte chemoattractant protein-1 [MCP-1]), in the brain. Elevated CCL2 levels are associated with cognitive impairment as well as the migration and invasion of glioblastoma cells. The present study hypothesized that non-toxic concentrations of Cd (as cadmium chloride [CdCl 2 ]) could up-regulate CCL2 production in U-87 MG human glio-blastoma cells. The results showed that after exposure of the U-87 MG cells to CdCl 2 at 1 and 10 mM, there was an up-regulation of CCL2 mRNA expression after 3 h of exposure and increased CCL2 secretion after 6 and 24 h. The study also found that inhibition of MAPK pathways, including ERK1/ 2, p38, and JNK by U0126, SB203580 and SP600125, respectively, reduced Cd-induced CCL2 secretion by the cells. Moreover, when cells were pretreated with Ro 32-0432 (an inhibitor of calcium-dependent PKC) and LY294002 (a PI3K inhibitor), this also resulted in a down-regulation of any Cd-induced CCL2 expression. Taken together, the results of this study allow for the conclusion to be made that CCL2 up-regulation in U-87 MG cells induced by Cd is mediated, in part, by an activation of MAPK, PI3K/Akt, and PKC pathways.

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“…Cd is a common component in many electronic devices, which includes batteries, solar cells, paints and pigments, however, it can also emanate to water sources through industrial waste and run‐offs [3]. Cadmium is a confirmed carcinogen, mutagen, and teratogen [4, 5] targeting liver, kidney, lungs or gastrointestinal tract upon accumulation. Therefore, efficient water treatment processes are required to be adopted to ensure that adverse effects on the environment are eradicated by reducing Cd to the minimum allowable discharge limit.…”

Section: Introductionmentioning

confidence: 99%

Facile synthesis and application of cellulosic coagulant from banana peels in cadmium‐spiked water

Oyewo

Bopape

2020

IET nanobiotechnol.

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In vitro and bioinformatics mechanistic-based approach for cadmium carcinogenicity understanding

Cited by 10 publications

References 79 publications

Insights into Cadmium-Induced Carcinogenesis through an In Vitro Study Using C3H10T1/2Cl8 Cells: The Multifaceted Role of Mitochondria

Insights into Cadmium-Induced Carcinogenesis through an In Vitro Study Using C3H10T1/2Cl8 Cells: The Multifaceted Role of Mitochondria

Cadmium induces CCL2 production in glioblastoma cells via activation of MAPK, PI3K, and PKC pathways

Facile synthesis and application of cellulosic coagulant from banana peels in cadmium‐spiked water

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