The interaction of disulfiram and H2S metabolism in inhibition of aldehyde dehydrogenase activity and liver cancer cell growth

Read, Ethan; Milford, Jarod; Zhu, Jiechun; Wu, Lingyun; Bilodeau, Marc; Yang, Guangdong

doi:10.1016/j.taap.2021.115642

Cited by 8 publications

(3 citation statements)

References 116 publications

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“…This is consistent with the highest levels of MT at the OVF site, which lacks ADH induction. This suggests that ADH could be inhibited by zinc chelators, such as sulfur compounds, and metal competitors, such as Cd [43,44], which abound in tire-and asphalt-wear particles in road/street runoff and overflow sites in urban areas.…”

Section: Discussionmentioning

confidence: 99%

Micro and Nanoplastic Contamination and Its Effects on Freshwater Mussels Caged in an Urban Area

Gagné,

Roubeau-Dumont,

André

et al. 2023

JoX

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Plastic-based contamination has become a major cause of concern as it pervades many environments such as air, water, sediments, and soils. This study sought to examine the presence of microplastics (MPs) and nanoplastics (NPs) in freshwater mussels placed at rainfall/street runoff overflows, downstream (15 km) of the city centre of Montréal, and 8 km downstream of a municipal effluent dispersion plume. MPs and NPs were determined using flow cytometry and size exclusion chromatography using fluorescence detection. Following 3 months of exposure during the summer season, mussels contained elevated amounts of both MPs and NPs. The rainfall overflow and downstream of the city centre were the most contaminated sites. Lipid peroxidation, metallothioneins, and protein aggregates (amyloids) were significantly increased at the most contaminated sites and were significantly correlated with NPs in tissues. Based on the levels of MPs and NPs in mussels exposed to municipal effluent, wastewater treatment plants appear to mitigate plastic contamination albeit not completely. In conclusion, the data support the hypothesis that mussels placed in urbanized areas are more contaminated by plastics, which are associated with oxidative damage. The highest responses observed at the overflow site suggest that tire wear and/or asphalt (road) erosion MPs/NPs represent important sources of contamination for the aquatic biota.

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Section: Discussionmentioning

confidence: 99%

Micro and Nanoplastic Contamination and Its Effects on Freshwater Mussels Caged in an Urban Area

Gagné,

Roubeau-Dumont,

André

et al. 2023

JoX

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“…Several lines of evidence suggest the anticancer activity of DSF with several mechanisms focused on elevating intracellular reactive oxygen species (ROS) levels [ 8–10 ], reducing acetaldehyde dehydrogenase (ALDH) expression to weaken the stemness of cancer cells [ 8 , 11–13 ], and disturbing the ubiquitin-proteasome system [ 14–16 ], or causing DNA damage [ 17 , 18 ]. These antitumor effects were reported in many preclinical studies and recently in several types of human cancer (prostate [ 19 ], liver [ 20 , 21 ], and ovarian cancer [ 8 ], glioblastoma [ 17 , 22 ], lung [ 23 ], breast [ 24 ], pancreatic [ 24 ], acute myeloid leukemia [ 9 ], melanoma [ 25 ], and GC [ 26 , 27 ])…”

Section: Introductionmentioning

confidence: 91%

Disulfiram/Copper induces antitumor activity against gastric cancer via the ROS/MAPK and NPL4 pathways

Liu

Guan²,

Wang

et al. 2022

Bioengineered

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Disulfiram (DSF) is an anti-alcoholism medication with superior antitumor activity and clinical safety; its antitumor mechanisms in gastric cancer (GC) have not been fully explored. In the present work, low nontoxic concentrations of copper (Cu) ions substantially enhanced DSF’s antitumor activity, inhibiting the proliferation and growth of GC cell lines. DSF/Cu elevated the generation of reactive oxygen species (ROS), and apoptosis was induced in an ROS-dependent manner. This process might involve primary inhibition GC by DSF/Cu through induction of apoptosis via the ROS/mitogen-activated protein kinase pathway. Disordering transportation of ubiquitinated protein may also fuel the process. In summary, we found that DSF exerts antitumor effects on GC. DSF/Cu should be considered as adjunctive therapy for GC.

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“…H 2 S can be involved in many liver diseases such as fibrosis, cirrhosis and liver cancer. [5][6] Several pathways are involved in the pathogenesis of ethanol-induced liver disease. One of the central pathways involves the induction of cytochrome P450 2E1 by ethanol, which leads to the induction of lipid peroxidation in hepatocytes.…”

Section: Introductionmentioning

confidence: 99%

Role of sulfide anion in the development of chronic alcoholic hepatitis under the conditions of modulation of adenosine monophosphate kinase – a correlational study

Mykytenko,

Akimov,

Shevchenko

et al. 2023

Eur J Clin Exp Med

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Introduction and aim. Hydrogen sulfide (H 2 S) has attracted the attention of researchers as a novel signaling molecule that affects vascular metabolism, immune function, stress and inflammation. It plays an important role in pathophysiological disorders under the conditions of the development of obesity, diabetes, non-alcoholic fatty liver disease and cardiovascular diseases. The purpose of this work is to establish correlation ratios of H 2 S concentration with markers of oxidative-nitrosative stress and extracellular matrix metabolism of the liver during chronic alcoholic hepatitis modeling and AMPK modulation by phenformin and doxorubicin. Material and methods. The experiments were performed on 36 white, sexually mature male Wistar rats, weighing 180-220 g. Alcoholic hepatitis was modelled by alcohol administration, on the background of alcoholic hepatitis animals received phenformin orally at a dose of 10 mg/kg or doxorubicin at a dose of 1.25 mg/kg intraperitoneally. Statistical processing of the results of biochemical studies was carried out using the non-parametric method of Spearman to determine correlations. Results. H 2 S during alcoholic hepatitis inversely proportionally strongly correlates with the concentration of nitrites, oxyproline and arginase activity. Phenformin administration during alcoholic hepatitis leads to formation of inversely proportionally strongly correlation of H 2 S with the production of superoxide anion radical, the concentration of malondialdehyde, activities of constitutive NO-synthases, nitrite reductases, nitrate reductases, and arginase. Doxorubicin administration during alcoholic hepatitis leads to formation of directly proportional strongly correlation of H 2 S with the activity of constitutive NO-synthases, nitrite reductases, nitrate reductases. Conclusion. Administration of phenformin or doxorubicin expands correlations between H 2 S and indicators of oxidative-nitrosative stress.

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The interaction of disulfiram and H2S metabolism in inhibition of aldehyde dehydrogenase activity and liver cancer cell growth

Abstract: Title of Thesis Titre de la thèseThe interaction of disulfiram and H2S metabolism in inhibition of aldehyde dehydrogenase activity and liver cancer cell growth Name of Candidate Nom du candidat Read, Ethan

Cited by 8 publications

References 116 publications

Micro and Nanoplastic Contamination and Its Effects on Freshwater Mussels Caged in an Urban Area

Micro and Nanoplastic Contamination and Its Effects on Freshwater Mussels Caged in an Urban Area

Disulfiram/Copper induces antitumor activity against gastric cancer via the ROS/MAPK and NPL4 pathways

Role of sulfide anion in the development of chronic alcoholic hepatitis under the conditions of modulation of adenosine monophosphate kinase – a correlational study

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