Disulfiram/copper causes ROS levels alteration, cell cycle inhibition, and apoptosis in acute myeloid leukaemia cell lines with modulation in the expression of related genes

Hassani, Saeed; Ghaffari, Parisa; Chahardouli, Bahram; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir; Alizadeh, Shaban; Ghaffari, Seyed H.

doi:10.1016/j.biopha.2018.01.109

Cited by 66 publications

(42 citation statements)

References 47 publications

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“…Recent studies showed that DSF/Cu induced NPL4 (an adapter of p97/VCP segregase) aggregation and induced a complex cellular phenotype, finally leading to cell death [11]. Moreover, DSF/Cu was reported to induce significant cell cycle arrest and apoptosis, cause the disturbance of the ROS balance, and activate the stress-related ROS-JNK pathway as well as downregulate the NF-E2-related factor-2 (Nrf2) and Nuclear factor-кB (NF-кB) pathways in some tumor cells [12][13][14]. In addition, the anticancer effect of DSF is also related to epigenetics [15].…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, DSF can be combined with antitumor drugs to enhance the antitumor effect [16,17]. These studies have highlighted the importance of DSF in antitumor therapy, such as acute myeloid leukemia, prostate cancer, non-small cell lung cancer, breast cancer and so on [13][14][15][16][17]. However, more research is needed on the role of DSF/Cu in NPC.…”

Section: Introductionmentioning

confidence: 99%

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Disulfiram/Copper Induces Antitumor Activity against Both Nasopharyngeal Cancer Cells and Cancer-Associated Fibroblasts through ROS/MAPK and Ferroptosis Pathways

Chen

et al. 2020

Cancers

132

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Disulfiram/copper (DSF/Cu) is a promising antitumor reagent for clinical application due to its excellent anticancer activity and safety. However, the anticancer mechanism of DSF/Cu has not been fully elucidated. Our study showed that DSF/Cu strongly induced cytotoxic effects on both nasopharyngeal carcinoma (NPC) cells and α-smooth muscle actin (α-SMA)-positive fibroblasts. Fluorescence activated cell sorting (FACS) analysis further showed that DSF/Cu induced a higher late apoptosis rate in α-SMA-positive fibroblasts than in tumor cells, and DSF/Cu promoted apoptosis and necrosis by an aldehyde dehydrogenase (ALDH)-independent method. Furthermore, we found that the antitumor activity of DSF/Cu against NPC cells occurred through ROS/MAPK and p53-mediated ferroptosis pathways, and that the ROS scavenger N-acetyl-l-cysteine (NAC) could reverse the cellular and lipid ROS levels. In 5-8F xenografts, both TUNEL and immunohistochemical (IHC) analyses indicated that DSF/Cu could induce apoptosis and inactivate cancer-associated fibroblasts (CAFs) by inhibiting the expression of α-SMA. In addition, combined with cisplatin (CDDP), DSF/Cu was well tolerated in vivo and could significantly suppress the growth of NPC tissues. Our study demonstrated that DSF/Cu induced antitumor activity against both tumor cells, as well as CAFs and suggested that the use of DSF/Cu as an adjunctive therapy for NPC is worthy of consideration.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Disulfiram/Copper Induces Antitumor Activity against Both Nasopharyngeal Cancer Cells and Cancer-Associated Fibroblasts through ROS/MAPK and Ferroptosis Pathways

Chen

et al. 2020

Cancers

132

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“…Copper is not of course a cause of cancer, but blocking of copper acquire can slow down formation of the new blood vessels and cancer progression became suppressed (133,134). Comparing to the research indicating that copper can be somewhat involved in a tumor progression, some studies contrary proved a protection to cancer by copper, which was mediated by supporting of enzymes such as: superoxide dismutase and others, where copper act as a cofactor (135)(136)(137).…”

Section: Various Pathways and Processesmentioning

confidence: 90%

Copper and copper nanoparticles toxicity and their impact on basic functions in the body

Pohanka¹

2019

BLL

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Copper is a biogenic metal having multiple functions in basic processes in organisms and it is common in all kingdoms of life. Limited intake of copper is a problem; however, doses of copper exceeding the recommended alimentary source are problematic as well and toxicity is soon manifested. Impact of copper nanoparticles on human health is another serious issue taken into consideration in this review. Regarding to copper toxicity, neurodegenerative disorders including Alzheimer and Parkinson diseases are suspected to be linked to copper toxicity or copper can contribute to their progression. Wilson and Menke diseases are also described as examples of copper intolerance. This paper is focused on the description, literature survey and discussion of the current knowledge about copper and copper nanoparticles toxicity and their involvement in various pathological processes (Tab. 6, Fig. 2, Ref. 171).

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“…It is of interest to note that disulfiram (DSF), which is used to treat alcohol dependency, also has an anti-cancer effect. A recently reported in vitro study using human AML cell lines, showed that DSF combined with copper increased the expression of reactive oxygen species (ROS), resulting in cell cycle arrest and AML cell apoptosis [20]. Also, the incidence of AML is increased in patients with autoimmune diseases, such as SLE, and is also increased after exposure to cytotoxic agents [21,22].…”

Section: Discussionmentioning

confidence: 99%

Weighted Gene Coexpression Network Analysis Identifies Cysteine-Rich Intestinal Protein 1 (CRIP1) as a Prognostic Gene Associated with Relapse in Patients with Acute Myeloid Leukemia

Xia

et al. 2019

Med Sci Monit

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BackgroundAcute myeloid leukemia (AML) is associated with a high relapse rate and poor prognosis. This study aimed to use weighted gene coexpression network analysis (WGCNA) of gene coexpression networks to identify candidate prognostic biomarker genes in patients with AML and to investigate the expression of these genes in the human U937 cell line in vitro.Material/MethodsRNA-seq data were retrieved from the Cancer Genome Atlas (TCGA) and included bone marrow samples and survival data of patients with AML (N=151), patients who did not relapse after treatment (N=119), and patients with relapse (N=40). Differentially expressed genes were identified, WGCNA was used to detect functional modules, and survival analysis was performed. The Cell Counting Kit-8 (CCK-8) assay investigated the proliferation of U937 cells transfected with short hairpin RNAs (shRNAs), shCRIP1, shHIST1H1C, and shHIST1H1E. RNA-seq analysis identified gene expression following CRIP1 knockdown.ResultsEighty-two genes were associated with both relapse and prognosis in patients with AML. There were two prognosis-related gene modules in the coexpression network. In the coexpression network, the histone cluster 1 H1 family member gene, HIST1H1C had the maximum relapse fold change, HIST1H1E had the lowest survival p-value, and the cysteine-rich intestinal protein 1 (CRIP1) gene had the most edge numbers and was significantly associated with poor prognosis (P=0.0165786). RNA-seq data showed that there was a significant difference in gene expression after CRIP1 knockdown in U937 cells.ConclusionsWGCNA of gene coexpression networks identified CRIP1 as a potential prognostic biomarker gene in patients with AML.

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Disulfiram/copper causes ROS levels alteration, cell cycle inhibition, and apoptosis in acute myeloid leukaemia cell lines with modulation in the expression of related genes

Cited by 66 publications

References 47 publications

Disulfiram/Copper Induces Antitumor Activity against Both Nasopharyngeal Cancer Cells and Cancer-Associated Fibroblasts through ROS/MAPK and Ferroptosis Pathways

Disulfiram/Copper Induces Antitumor Activity against Both Nasopharyngeal Cancer Cells and Cancer-Associated Fibroblasts through ROS/MAPK and Ferroptosis Pathways

Copper and copper nanoparticles toxicity and their impact on basic functions in the body

Weighted Gene Coexpression Network Analysis Identifies Cysteine-Rich Intestinal Protein 1 (CRIP1) as a Prognostic Gene Associated with Relapse in Patients with Acute Myeloid Leukemia

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