Cadmium and molybdenum co-induce pyroptosis via ROS/PTEN/PI3K/AKT axis in duck renal tubular epithelial cells

Zhang, Caiying; Lin, Tianjin; Nie, Guoxing; Hu, Ruiming; Pi, Shaoxing; Wei, Zejing; Wang, Chang; Xing, Chenghong; Hu, Guoliang

doi:10.1016/j.envpol.2020.116403

Cited by 84 publications

(37 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ROS-induced damage results in cytotoxicity through mitochondrial damage and promotion of apoptosis (Jeng and Swanson 2006). The observations are in agreement with previous investigations of one of us (SS) and other investigations in duck renal tubular epithelial cells demonstrating the induction of oxidative stress by tungstate and molybdate in various organs such as the kidneys and the liver, overwhelming the cellular antioxidant defense (Sachdeva et al 2013;Shi et al 2017;Wang et al 2020;Zhang et al 2021).…”

Section: Discussionsupporting

confidence: 90%

Comparative outcomes of exposing human liver and kidney cell lines to tungstate and molybdate

Sachdeva

Maret

2021

Toxicology Mechanisms and Methods

View full text Add to dashboard Cite

Tungsten has no known function in humans and is a relatively new contaminant, whereas molybdenum, its congener in the periodic table, is a nutritionally essential element. In addition to early studies on molybdosis in ruminants, their toxic effects in the form of tungstate and molybdate have been addressed primarily in rodents and are predominantly mediated by inducing oxidative stress in various tissues. The purpose of this study was to evaluate the differences between tungstate and molybdate in human liver (HepG2) and kidney (HEK293) cell lines in terms of retention in cells, effect on reactive oxygen species, and activities of xanthine oxidase and phosphatases. The cell lines were exposed to tungstate or molybdate (1 mM to 10 mM) for 24 h, lysed and analyzed for the above biochemical parameters. Despite the chemical similarity of the two anions, cell-specific differential effects were observed. At all concentrations, tungstate was retained more in HEK293 cells while molybdate was retained more in HepG2 cells. HepG2 cells were more sensitive to tungstate than molybdate, showing reduced viability at concentrations as low as 10 mM. Exposure to either anion resulted in the inhibition of protein tyrosine phosphatases at 1 mM and an increased production of reactive oxygen species (ROS) at 100 mM despite their inhibition of the ROS-producing molybdenum enzyme xanthine oxidase. In conclusion, the results indicate that excess of nutritionally essential molybdate or non-essential tungstate causes toxicity by affecting ROS-and phosphorylation-dependent signaling pathways and ensuing gene expression.

show abstract

Section: Discussionsupporting

confidence: 90%

Comparative outcomes of exposing human liver and kidney cell lines to tungstate and molybdate

Sachdeva

Maret

2021

Toxicology Mechanisms and Methods

View full text Add to dashboard Cite

show abstract

“…Previously, it was discussed that Akt phosphorylation and activation can promote cancer progression and induce chemoresistance [221,222]. Interestingly, ROS can function as an upstream mediator of Akt signaling [223,224]. Piperlongumine as an anti-tumor agent, promotes ROS levels and accumulation in lung cancer cells to suppress Akt signaling, leading to CP sensitivity [225].…”

Section: Therapeutic Targetingmentioning

confidence: 99%

Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

et al. 2021

View full text Add to dashboard Cite

The failure of chemotherapy is a major challenge nowadays, and in order to ensure effective treatment of cancer patients, it is of great importance to reveal the molecular pathways and mechanisms involved in chemoresistance. Cisplatin (CP) is a platinum-containing drug with anti-tumor activity against different cancers in both pre-clinical and clinical studies. However, drug resistance has restricted its potential in the treatment of cancer patients. CP can promote levels of free radicals, particularly reactive oxygen species (ROS) to induce cell death. Due to the double-edged sword role of ROS in cancer as a pro-survival or pro-death mechanism, ROS can result in CP resistance. In the present review, association of ROS with CP sensitivity/resistance is discussed, and in particular, how molecular pathways, both upstream and downstream targets, can affect the response of cancer cells to CP chemotherapy. Furthermore, anti-tumor compounds, such as curcumin, emodin, chloroquine that regulate ROS and related molecular pathways in increasing CP sensitivity are described. Nanoparticles can provide co-delivery of CP with anti-tumor agents and by mediating photodynamic therapy, and induce ROS overgeneration to trigger CP sensitivity. Genetic tools, such as small interfering RNA (siRNA) can down-regulate molecular pathways such as HIF-1α and Nrf2 to promote ROS levels, leading to CP sensitivity. Considering the relationship between ROS and CP chemotherapy, and translating these findings to clinic can pave the way for effective treatment of cancer patients.

show abstract

“…Although Cd can induce gene mutation indirectly and promote the development of cancer, a global picture of the progression of adenocarcinoma after long-term exposure to low-dose Cd is still vague. Previous studies have reported that cadmium affected the biological behavior of cells through Wnt ( 23 , 24 ), PI3K/AKT ( 25 , 26 ) or JNK ( 5 , 27 ) signaling pathways, but there is still a lack of studies on the effect of long-term, low dose cadmium exposure on whole exome and transcriptomes of lung cancer cells in the lung. Cadmium itself has the ability to induce gene mutation indirectly ( 28 ) and, therefore, it inhibits the DNA repair system, which results in gene damage and accumulation of mutation.…”

Section: Discussionmentioning

confidence: 99%

Multiomics Landscape Uncovers the Molecular Mechanism of the Malignant Evolution of Lung Adenocarcinoma Cells to Chronic Low Dose Cadmium Exposure

et al. 2021

View full text Add to dashboard Cite

Cadmium (Cd) from cigarette smoke and polluted air can lead to lung adenocarcinoma after long-term inhalation. However, most studies are based on short-term exposure to this toxic metal at high concentrations. Here, we investigate the effects of long-term exposure of A549 cells (lung adenocarcinoma) to cadmium at low concentrations using morphological and multiomics analyses. First, we treated A549 cells continuously with CdCl2 at 1μM for 8 months and found that CdCl2 promoted cellular migration and invasion. After that, we applied transmission electron and fluorescence microscopies and did not observe significant morphological changes in Golgi apparatus, endoplasmic reticulum, lysosomes, or mitochondria on Cd treated cells; microfilaments, in contrast, accumulated in lamellipodium and adhesion plaques, which suggested that Cd enhanced cellular activity. Second, by using whole-exome sequencing (WES) we detected 4222 unique SNPs in Cd-treated cells, which included 382 unique non-synonymous mutation sites. The corresponding mutated genes, after GO and KEGG enrichments, were involved mainly in cell adhesion, movement, and metabolic pathways. Third, by RNA-seq analysis, we showed that 1250 genes (784 up and 466 down), 1623 mRNAs (1023 up and 591 down), and 679 lncRNAs (375 up and 304 down) were expressed differently. Furthermore, GO enrichment of these RNA-seq results suggested that most differentially expressed genes were related to cell adhesion and organization of the extracellular matrix in biological process terms; KEGG enrichment revealed that the differentially expressed genes took part in 26 pathways, among which the metabolic pathway was the most significant. These findings could be important for unveiling mechanisms of Cd-related cancers and for developing cancer therapies in the future.

show abstract

Cadmium and molybdenum co-induce pyroptosis via ROS/PTEN/PI3K/AKT axis in duck renal tubular epithelial cells

Cited by 84 publications

References 76 publications

Comparative outcomes of exposing human liver and kidney cell lines to tungstate and molybdate

Comparative outcomes of exposing human liver and kidney cell lines to tungstate and molybdate

Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

Multiomics Landscape Uncovers the Molecular Mechanism of the Malignant Evolution of Lung Adenocarcinoma Cells to Chronic Low Dose Cadmium Exposure

Contact Info

Product

Resources

About