Cadmium‐induced malignant transformation in rat liver cells: Role of aberrant oncogene expression and minimal role of oxidative stress

Qu, Wei; Diwan, Bhalchandra A.; Reece, Jeffrey M.; Bortner, Carl D.; Pi, Jingbo; Liu, Jie; Waalkes, Michael P.

doi:10.1002/ijc.20736

Cited by 63 publications

(55 citation statements)

References 36 publications

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“…At the beginning, ROS production rose, only to drop back to normal after eight weeks of exposure (48). It has been shown that ROS production does not play an essential role in chronic Cd-induced malignant transformation in rat liver cells (49).…”

Section: Role Of Cadmium In Oxidative Stress Inductionmentioning

confidence: 99%

Cadmium Toxicity Revisited: Focus on Oxidative Stress Induction and Interactions with Zinc and Magnesium

Matović

Buha

Bulat

et al. 2011

Archives of Industrial Hygiene and Toxicology

184

122

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Discovered in late 1817, cadmium is currently one of the most important occupational and environmental pollutants. It is associated with renal, neurological, skeletal and other toxic effects, including reproductive toxicity, genotoxicity, and carcinogenicity. There is still much to fi nd out about its mechanisms of action, biomarkers of critical effects, and ways to reduce health risks. At present, there is no clinically effi cient agent to treat cadmium poisoning due to predominantly intracellular location of cadmium ions. This article gives a brief review of cadmium-induced oxidative stress and its interactions with essential elements zinc and magnesium as relevant mechanisms of cadmium toxicity. It draws on available literature data and our own results, which indicate that dietary supplementation of either essential element has benefi cial effect under condition of cadmium exposure. We have also tackled the reasons why magnesium addition prevails over zinc and discussed the protective role of magnesium during cadmium exposure. These fi ndings could help to solve the problem of prophylaxis and therapy of increased cadmium body burden.

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Section: Role Of Cadmium In Oxidative Stress Inductionmentioning

confidence: 99%

Cadmium Toxicity Revisited: Focus on Oxidative Stress Induction and Interactions with Zinc and Magnesium

Matović

Buha

Bulat

et al. 2011

Archives of Industrial Hygiene and Toxicology

184

122

View full text Add to dashboard Cite

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“…Cd also accumulates in renal cortex, leading to induction of renal cancer (Kolonel, 1976;Il'yasova and Schwartz, 2005;Hu et al, 2002). Furthermore, rat liver epithelial cells could undergo carcinogenic transformation after chronic, low-level Cd exposure, suggesting the involvement of Cd in liver tumor formation (Qu et al, 2005). Cd exposure is also related to prostate, breast, bladder, pancreatic cancers (Goyer et al, 2004;Kellen et al, 2007;Sens et al, 2004;Schwartz and Reis, 2000;McElroy et al, 2006), and gallbladder cancer where Cd is concentrated after secretion by liver (Pandey, 2006;Waalkes, 2003).…”

Section: Introductionmentioning

confidence: 99%

Disulfiram promotes the conversion of carcinogenic cadmium to a proteasome inhibitor with pro-apoptotic activity in human cancer cells

Yang

Chen

et al. 2008

Toxicology and Applied Pharmacology

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The ubiquitinproteasome system is involved in various cellular processes, including transcription, apoptosis, and cell cycle. In vitro, in vivo, and clinical studies suggest the potential use of proteasome inhibitors as anticancer drugs. Cadmium (Cd) is a widespread environmental pollutant that has been classified as a human carcinogen. Recent study in our laboratory suggested that the clinically used anti-alcoholism drug disulfiram (DSF) could form a complex with tumor cellular copper, resulting in inhibition of the proteasomal chymotrypsin-like activity and induction of cancer cell apoptosis. In the current study, we report, for the first time, that DSF is able to convert the carcinogen Cd to a proteasome-inhibitor and cancer cell apoptosis inducer. Although the DSFCd complex inhibited the chymotrypsin-like activity of a purified 20S proteasome with an IC 50 value of 32 μmol/L, this complex was much more potent in inhibiting the chymotrypsin-like activity of prostate cancer cellular 26S proteasome. Inhibition of cellular proteasome activity by the DSF-Cd complex resulted in the accumulation of ubiquitinated proteins and the natural proteasome substrate p27, which was followed by activation of calpain and induction of apoptosis. Importantly, human breast cancer MCF10DCIS cells were much more sensitive to the DSF-Cd treatment than immortalized but non-tumorigenic human breast MCF-10A cells, demonstrating that the DSF-Cd complex could selectively induce proteasome inhibition and apoptosis in human tumor cells. Our work suggests the potential use of DSF for treatment of cells with accumulated levels of carcinogen Cd.

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“…A 10-fold increase in expression levels of the oncogenes c-myc and c-jun together with change in DNA methylation state was observed in the transformation of the TRL1215 rat liver epithelial cells (Takiguchi et al 2003;Qu et al 2005). Global DNA hypomethylation and over expression of c-myc and k-ras were observed in cadmium-induced transformation of the MCF-10 human breast epithelial cells estrogen receptor (ER)-negative to ER-positive breast cancer cells (BenbrahimTallaa et al 2009).…”

Section: Epigenetic Effects and Metabolic Adaptationmentioning

confidence: 99%

“…The human cell lines shown to be susceptible to carcinogenic effects of cadmium include the RWPE-1 prostate epithelial cells (Achanzar et al 2001), UROtsa uroepithelial cells (Sens et al 2004), the MCF-10A breast epithelial cells (BenbrahimTallaa et al 2009), the BEAS-2B bronchial epithelial cells (Jing et al 2012), and pancreatic ductal epithelial cells (Qu et al 2012). Animal cell lines found to be susceptible to cadmium carcinogenicity included the rat liver epithelial TRL1215 cell line (Takiguchi et al 2003;Qu et al 2005).…”

Section: Metallothionein Sequestration and Cadmium's Long Half-lifementioning

confidence: 99%

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Emerging Roles of Cadmium and Heme Oxygenase in Type-2 Diabetes and Cancer Susceptibility

Satarug

2012

Tohoku J. Exp. Med.

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Many decades after an outbreak of severe cadmium poisoning, known as Itai-itai disease, cadmium continues to pose a significant threat to human health worldwide. This review provides an update on the effects of this environmental toxicant cadmium, observed in numerous populations despite modest exposure levels. In addition, it describes the current knowledge on the link between heme catabolism and glycolysis. It examines novel functions of heme oxygenase-2 (HO-2) that protect against type 2-diabetes and obesity, which have emerged from diabetic/obese phenotypes of the HO-2 knockout mouse model. Increased cancer susceptibility in type-2 diabetes has been noted in several large cohorts. This is a cause for concern, given the high prevalence of type-2 diabetes worldwide. A lifetime exposure to cadmium is associated with pre-diabetes, diabetes, and overall cancer mortality with sex-related differences in specific types of cancer. Liver and kidney are target organs for the toxic effects of cadmium. These two organs are central to the maintenance of blood glucose levels. Further, inhibition of gluconeogenesis is a known effect of heme, while cadmium has the propensity to alter heme catabolism. This raises the possibility that cadmium may mimic certain HO-2 deficiency conditions, resulting in diabetic symptoms. Intriguingly, evidence has emerged from a recent study to suggest the potential interaction and co-regulation of HO-2 with the key regulator of glycolysis: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4). HO-2 could thus be critical to a metabolic switch to cancer-prone cells because the enzyme PFKFB and glycolysis are metabolic requirements for cell proliferation and resistance to apoptosis.

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Cadmium‐induced malignant transformation in rat liver cells: Role of aberrant oncogene expression and minimal role of oxidative stress

Cited by 63 publications

References 36 publications

Cadmium Toxicity Revisited: Focus on Oxidative Stress Induction and Interactions with Zinc and Magnesium

Cadmium Toxicity Revisited: Focus on Oxidative Stress Induction and Interactions with Zinc and Magnesium

Disulfiram promotes the conversion of carcinogenic cadmium to a proteasome inhibitor with pro-apoptotic activity in human cancer cells

Emerging Roles of Cadmium and Heme Oxygenase in Type-2 Diabetes and Cancer Susceptibility

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