Oxidative Stress in Cancer

Hayes, John D.; Dinkova‐Kostova, Albena T.; Tew, Kenneth D.

doi:10.1016/j.ccell.2020.06.001

Cited by 1,537 publications

(1,257 citation statements)

References 305 publications

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“…Cancer cells and tissues exist under persistent oxidative stress, which affects their survival and metastatic properties [ 19 ]. Therefore, we were interested in whether DEA has any effect on ROS formation in the B16F10 melanoma line.…”

Section: Resultsmentioning

confidence: 99%

Involvement of Mitochondrial Mechanisms in the Cytostatic Effect of Desethylamiodarone in B16F10 Melanoma Cells

Ramadan

Szabó

Kovács

et al. 2020

IJMS

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Previously, we showed that desethylamiodarone (DEA), a major metabolite of the widely used antiarrhythmic drug amiodarone, has direct mitochondrial effects. We hypothesized that these effects account for its observed cytotoxic properties and ability to limit in vivo metastasis. Accordingly, we examined DEA’s rapid (3–12 h) cytotoxicity and its early (3–6 h) effects on various mitochondrial processes in B16F10 melanoma cells. DEA did not affect cellular oxygen radical formation, as determined using two fluorescent dyes. However, it did decrease the mitochondrial transmembrane potential, as assessed by JC-1 dye and fluorescence microscopy. It also induced mitochondrial fragmentation, as visualized by confocal fluorescence microscopy. DEA decreased maximal respiration, ATP production, coupling efficiency, glycolysis, and non-mitochondrial oxygen consumption measured by a Seahorse cellular energy metabolism analyzer. In addition, it induced a cyclosporine A–independent mitochondrial permeability transition, as determined by Co2+-mediated calcein fluorescence quenching measured using a high-content imaging system. DEA also caused outer mitochondrial membrane permeabilization, as assessed by the immunoblot analysis of cytochrome C, apoptosis inducing factor, Akt, phospho-Akt, Bad, and phospho-Bad. All of these data supported our initial hypothesis.

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Section: Resultsmentioning

confidence: 99%

Involvement of Mitochondrial Mechanisms in the Cytostatic Effect of Desethylamiodarone in B16F10 Melanoma Cells

Ramadan

Szabó

Kovács

et al. 2020

IJMS

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“…NAFLD begins with aberrant triglyceride accumulation in the liver and may progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and HCC. Oxidative stress has been proposed as the major actor involved in NAFLD-NASH pathogenesis [ 6 , 68 , 69 , 70 ].…”

Section: Nrf2 In Chronic Liver Injurymentioning

confidence: 99%

“…Under oxidative stress, such as exposure to reactive oxygen species (ROS) or electrophiles, Keap1 undergoes conformational modifications, resulting in the loss of interaction between Nrf2 and Keap1 [ 4 , 5 , 6 ]. As a consequence, Nrf2 is not degraded, but moves to the nucleus where it promotes transcription of a number of genes involved in cellular protection, including phase I (such as NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase (HO)-1), phase II (glutathione S -transferase (GST)), and phase III enzymes [ 6 , 7 , 8 , 9 ]. By modulating a wide range of cell defense processes, Nrf2 enhances the cell’s capability to counteract harmful substances.…”

Section: Introductionmentioning

confidence: 99%

Nrf2 in Neoplastic and Non-Neoplastic Liver Diseases

Orrù

Giordano

Columbano

2020

Cancers

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Activation of the Keap1/Nrf2 pathway, the most important cell defense signal, triggered to neutralize the harmful effects of electrophilic and oxidative stress, plays a crucial role in cell survival. Therefore, its ability to attenuate acute and chronic liver damage, where oxidative stress represents the key player, is not surprising. On the other hand, while Nrf2 promotes proliferation in cancer cells, its role in non-neoplastic hepatocytes is a matter of debate. Another topic of uncertainty concerns the nature of the mechanisms of Nrf2 activation in hepatocarcinogenesis. Indeed, it remains unclear what is the main mechanism behind the sustained activation of the Keap1/Nrf2 pathway in hepatocarcinogenesis. This raises doubts about the best strategies to therapeutically target this pathway. In this review, we will analyze and discuss our present knowledge concerning the role of Nrf2 in hepatic physiology and pathology, including hepatocellular carcinoma. In particular, we will critically examine and discuss some findings originating from animal models that raise questions that still need to be adequately answered.

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Section: Introductionmentioning

confidence: 99%

“…Oxidative stress, which is the excessive accumulation of reactive oxygen species (ROS), is an important factor in cancer development and progression [ 1 ]. Therefore, cells provide specific antioxidant defense systems to scavenge ROS and to limit damage to proteins, nucleic acids, and lipids [ 1 ]. One of such systems is the thioredoxin system, which includes thioredoxin (TRX), thioredoxin reductase (TrxR), α-nicotinamide adenine dinucleotide phosphate (NADPH), and thioredoxin interacting protein (TXNIP) [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Thioredoxin Interacting Protein (TXNIP) Is Differentially Expressed in Human Tumor Samples but Is Absent in Human Tumor Cell Line Xenografts: Implications for Its Use as an Immunosurveillance Marker

Schröder

Schumacher

Böckelmann

2020

Cancers

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Thioredoxin interacting protein (TXNIP) is a metabolic protein critically involved in redox homeostasis and has been proposed as a tumor suppressor gene in a variety of malignancies. Accordingly, TXNIP is downregulated in breast, bladder, and gastric cancer and in tumor transplant models TXNIP overexpression inhibits growth and metastasis. As TXNIP protein expression has only been investigated in few malignancies, we employed immunohistochemical detection in a large multi-tumor tissue microarray consisting of 2,824 samples from 94 different tumor entities. In general, TXNIP protein was present only in a small proportion of primary tumor samples and in these cases was differently expressed depending on tumor stage and subtype (e.g., renal cell carcinoma, thyroid cancer, breast cancer, and ductal pancreatic cancer). Further, TXNIP protein expression was determined in primary mouse xenograft tumors derived from human cancer cell lines and was immunohistochemically absent in all xenograft tumors investigated. Intriguingly, TXNIP expression became gradually lower in the proximity of the primary tumor tissue and was absent in leukocytes directly adjacent to tumor tissue. In conclusion, these findings suggest that TXNIP downregulation is as a common feature in human tumor xenograft models and that intra-tumoral leukocytes down-regulate TXNIP. Hence TXNIP expression might be used to monitor the functional state of tumor-infiltrating leukocytes in tissue sections.

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Oxidative Stress in Cancer

Cited by 1,537 publications

References 305 publications

Involvement of Mitochondrial Mechanisms in the Cytostatic Effect of Desethylamiodarone in B16F10 Melanoma Cells

Involvement of Mitochondrial Mechanisms in the Cytostatic Effect of Desethylamiodarone in B16F10 Melanoma Cells

Nrf2 in Neoplastic and Non-Neoplastic Liver Diseases

Thioredoxin Interacting Protein (TXNIP) Is Differentially Expressed in Human Tumor Samples but Is Absent in Human Tumor Cell Line Xenografts: Implications for Its Use as an Immunosurveillance Marker

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