Copper toxicity affects proliferation and viability of human hepatoma cells (HepG2 line)

Aston, Nicola S.; Watt, Nicole T.; Morton, I E; Tanner, M S; Evans, Gareth S

doi:10.1191/096032700678815963

Cited by 73 publications

(45 citation statements)

References 35 publications

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“…2]. HaCaT cell line Vs Copper oxychloride [28][29][30]. This study supported to the observations where the copper oxychloride was less toxic to HepG2 cells at 20 µg/ml leaving 58.53% viable cells.…”

Section: Mtt Cell Viability Assaysupporting

confidence: 80%

In-vitro Assessment of Carbendazim and Copper oxychloride cytotoxicity on HaCaT and HepG2 human cell lines

2017

J App Biol Biotech

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The objective of present study was to evaluate the cytotoxic effect of two fungicides i.e. carbendazim and copper oxychloride on human cell lines HaCaT [keratinocyte] and HepG2 [hepatoma cell line]. The cytotoxic study was done by following the standard MTT [3-[4,5-dimethylthiazol-2-yl]-2,5-diphehyltetrazolium bromide] assay along with standard drug. The MTT assay results showed that these two fungicides showed concentration dependent cytotoxicity, upon incubation for 24 hours with concentration ranging 20-450 µg/ml and IC50 values were determined. The cell viability of HaCaT cells decreased from 100% to 35.86% with increase in carbendazim concentration 20-450 µg/ml. Whereas HepG2 cells were sensitive towards Carbendazim treatment with the decrease in viability up to 30.98% at 450 μg/ml. Copper oxychloride was more lethal, causing total cell death of HaCaT cells at 350 μg/ml, and HepG2 at 450 μg/ml and the present work correlate this toxicity caused by these two fungicides on human skin and liver. The study u nveils the cytotoxic effects of these fungicides on the skin as well as on the liver indicating the long term exposure to these compounds may lead to deleterious effects. Further study is needed on to identify the mechanism and pathway involved in the cytotoxic activity of these fungicides on HaCaT and HepG2 cell lines.

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Section: Mtt Cell Viability Assaysupporting

confidence: 80%

In-vitro Assessment of Carbendazim and Copper oxychloride cytotoxicity on HaCaT and HepG2 human cell lines

2017

J App Biol Biotech

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“…Excess Cu in cells is thought to interact non-specifically with various macromolecules, modify their conformation or cause site-specific damage (Burkitt 1994;Grillo et al 2010;Kang et al 2004;Letelier et al 2005). The resulting disruption of fundamental cellular processes triggers apoptosis (Araya et al 2003;Aston et al 2000;Grillo et al 2009;Hayashi et al 2006;Obata et al 1996;Prasad et al 1996;Singh et al 2006). However, threshold limits of Cu accumulation beyond which cellular damage is triggered, as demonstrated in Wilson and Menkes disease models having abnormal Cu accumulation, varies between different cell types (hepatocytes, neurons, and kidney cells) (Aston et al 2000;Hayashi et al 2006).…”

Section: Introductionmentioning

confidence: 95%

“…In either case, cells take up Cu ions, and when the uptake crosses a threshold limit, the cells become apoptotic and die (Araya et al 2003;Aston et al 2000;Grillo et al 2009;Hayashi et al 2006;Obata et al 1996;Prasad et al 1996;Singh et al 2006). The entire genital tract is reported to be exposed to 25-80 μg/day of Cu 2+ ions released from an inserted CuIUD (Arancibia et al 2003;Kjaer et al 1993).…”

Section: Introductionmentioning

confidence: 95%

Concentration-dependent cytotoxicity of copper ions on mouse fibroblasts in vitro: effects of copper ion release from TCu380A vs TCu220C intra-uterine devices

Cao

Zheng

et al. 2012

Biomed Microdevices

114

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Sustained release of copper (Cu) ions from Cu-containing intrauterine devices (CuIUD) is quite efficient for contraception. However, the tissue surrounding the CuIUD is exposed to toxic Cu ion levels. The objective for this study was to quantify the concentration dependent cytotoxic effects of Cu ions and correlate the toxicity due to Cu ion burst release for two popular T-shaped IUDs - TCu380A and TCu220C on L929 mouse fibroblasts. Fibroblasts were cultured in 98 well tissue culture plates and 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphehyltetrazolium bromide (MTT) assay was used to determine their viability and proliferation as a function of time. For cell seeding numbers ranging from 10,000 to 100,000, a maximum culture time of 48 h was identified for fibroblasts without significant reduction in cell proliferation due to contact inhibition. Thus, for Cu cytotoxicity assays, a cell seeding density of 50,000 and a maximum culture time of 48 h in 96 well plates were used. 24 h after cell seeding, culture media were replaced with Cu ion containing media solutions of different concentrations, including 24 and 72 h extracts from TCuIUDs and incubated for a further 24 h. Cell viability decreased with increasing Cu ion concentration, with 30 % and 100 % reduction for 40 μg/ml and 100 μg/ml respectively at 24 h. The cytotoxic effects were further evaluated using light microscopy, apoptosis and cell cycle analysis assays. Fibroblasts became rounded and eventually detached from TCP surface due to Cu ion toxicity. A linear increase in apoptotic cell population with increasing Cu ion concentration was observed in the tested range of 0 to 50 μg/ml. Cell cycle analysis indicated the arrest of cell division for the tested 25 to 50 μg/ml Cu ion treatments. Among the TCuIUDs, TCu220C having 265 mm(2) Cu surface area released 9.08 ± 0.16 and 26.02 ± 0.25 μg/ml, while TCu380A having 400 mm(2) released 96.7 ± 0.11 and 159.3 ± 0.15 μg/ml respectively following 24 and 72 h extractions. The effects of TCuIUD extracts on viability, morphology, apoptosis and cell cycle assay on L929 mouse fibroblasts cells, were appropriate for their respective Cu ion concentrations. Thus, a concentration of about 46 μg/ml (~29 μM) was identified as the LD50 dose for L929 mouse fibroblasts when exposed for 24 h based on our MTT cell viability assay. The burst release of lethal concentration of Cu ions from TCu380A, especially at the implant site, is a cause of concern, and it is advisable to use TCuIUD designs that release Cu ions within cytotoxic limits yet therapeutic, similar to TCu220C.

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“…When HepG2 cells are exposed to toxic concentrations of copper, there is a delay in cell cycle progression and an increase in cell death (7). In trout hepatocytes, copper exposure leads to cell death through ROS formation (46).…”

Section: Molecular Mechanisms Of Copper Toxicitymentioning

confidence: 99%

Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper

Song

Freedman

2009

Physiological Genomics

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Copper is an essential trace element; however, at supraphysiological levels, it can be extremely toxic. Microarray data from HepG2 cells exposed to 100, 200, 400, and 600 μM copper for 4, 8, 12 and 24 h were generated and analyzed. Principal components, K-means, and hierarchical clustering, interactome, and pathway mapping analyses indicated that these exposure conditions induce physiological and toxicological changes in the HepG2 transcriptome. As a general trend, when the level of toxicity increases, the number and diversity of affected genes, Gene Ontology categories, regulatory pathways, and complexity of interactomes increase. Physiological responses to copper include transition metal ion binding and responses to stress/stimulus, whereas toxicological responses include apoptosis, morphogenesis, and negative regulation of biomolecule metabolism. The global gene expression profile was overlaid onto biomolecular interaction networks and signal transduction cascades using pathway mapping and interactome identification. This analysis indicated that copper modulates signal transduction pathways associated with MAPK, NF-κB, death receptor, IGF-I, hypoxia, IL-10, IL-2, IL-6, EGF, Toll-like receptor, protein ubiquitination, xenobiotic metabolism, leukocyte extravasation, complement and coagulation, and sonic hedgehog signaling. These results provide insights into the global and molecular mechanisms regulating the physiological and toxicological responses to metal exposure.

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Copper toxicity affects proliferation and viability of human hepatoma cells (HepG2 line)

Cited by 73 publications

References 35 publications

In-vitro Assessment of Carbendazim and Copper oxychloride cytotoxicity on HaCaT and HepG2 human cell lines

In-vitro Assessment of Carbendazim and Copper oxychloride cytotoxicity on HaCaT and HepG2 human cell lines

Concentration-dependent cytotoxicity of copper ions on mouse fibroblasts in vitro: effects of copper ion release from TCu380A vs TCu220C intra-uterine devices

Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper

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