Read by QxMD icon Read


Jong-Lyel Roh, Hye Jin Jang, Eun Hye Kim, Daiha Shin
AIMS: The glutathione (GSH), thioredoxin (Trx), and Nrf2 systems represent a major defense against reactive oxygen species (ROS), the cellular imbalance of which in cancer promotes growth and therapeutic resistance. This study investigated whether targeting the GSH, Trx, and Nrf2 antioxidant systems effectively eliminated head and neck cancer (HNC). RESULTS: At high concentrations, auranofin, but not buthionine sulfoximine (BSO) alone, decreased the viability of HNC, whereas even at low concentrations, auranofin plus BSO synergized to kill HNC cells...
October 12, 2016: Antioxidants & Redox Signaling
Silvia Cellone Trevelin, Célio Xavier Dos Santos, Raphael Gomes Ferreira, Larissa de Sá Lima, Rangel Leal Silva, Cristoforo Scavone, Rui Curi, José Carlos Alves-Filho, Thiago Mattar Cunha, Pérsio Roxo-Júnior, Maria-Célia Cervi, Francisco Rafael Martins Laurindo, John Stephen Hothersall, Andrew M Cobb, Min Zhang, Aleksandar Ivetic, Ajay M Shah, Lucia Rossetti Lopes, Fernando Queiroz Cunha
The reactive-oxygen-species-(ROS)-generating-enzyme Nox2 is essential for leukocyte anti-microbial activity. However its role in cellular redox homeostasis and, consequently, in modulating intracellular signaling pathways remains unclear. Herein, we show Nox2 activation favors thioredoxin-1 (TRX-1)/p40phox interaction, which leads to exclusion of TRX-1 from the nucleus. In contrast, the genetic deficiency of Nox2 or its pharmacological inhibition with apocynin (APO) results in reductive stress after lipopolysaccharide-(LPS)-cell stimulation, which causes nuclear accumulation of TRX-1 and enhanced transcription of inflammatory mediators through nuclear-factor-(NF)-κB...
October 4, 2016: Scientific Reports
Deepu Oommen, Nicholas J F Dodd, Dennis Yiannakis, Rana Moyeed, Awadhesh N Jha
Auranofin, an organogold compound classified as an anti-rheumatic agent is under phase 2 clinical trials for re-purposing to treat recurrent epithelial ovarian cancer. We have reported earlier that Breast cancer 1, early onset (BRCA1) mutant ovarian cancer cells exhibit increased sensitivity to auranofin. BRCA1 is a DNA repair protein whose functional status is critical in the prognosis of ovarian cancer. Apart from DNA repair capability of cancer cells, membrane fluidity is also implicated in modulating resistance to chemotherapeutics...
October 2016: Mutation Research
Samuel N Rodman, Jacquelyn M Spence, Tyler J Ronnfeldt, Yueming Zhu, Shane R Solst, Rebecca A O'Neill, Bryan G Allen, Xiangming Guan, Douglas R Spitz, Melissa A Fath
The goal of this study was to determine if depletion of glutathione (GSH) and inhibition of thioredoxin (Trx) reductase (TrxR) activity could enhance radiation responses in human breast cancer stem cells by a mechanism involving thiol-dependent oxidative stress. The following were used to inhibit GSH and Trx metabolism: buthionine sulfoximine (BSO), a GSH synthesis inhibitor; sulfasalazine (SSZ), an inhibitor of xc(-) cysteine/glutamate antiporter; auranofin (Au), a thioredoxin reductase inhibitor; or 2-AAPA, a GSH-reductase inhibitor...
September 19, 2016: Radiation Research
Le Zhang, Qing Cheng, Longjie Zhang, Yijun Wang, Gary F Merrill, Tal Ilani, Deborah Fass, Elias S J Arnér, Jinsong Zhang
Increased thioredoxin reductase (TrxR) levels in serum were recently identified as possible prognostic markers for human prostate cancer or hepatocellular carcinoma. We had earlier shown that serum levels of TrxR protein are very low in healthy mice, but can in close correlation to alanine aminotransferase (ALT) increase more than 200-fold upon chemically induced liver damage. We also found that enzymatic TrxR activity in serum is counteracted by a yet unidentified oxidase activity in serum. In the present study we found that mice carrying H22 hepatocellular carcinoma tumors present highly increased levels of TrxR in serum, similarly to that reported in human patients...
August 28, 2016: Free Radical Biology & Medicine
Maneet Bhatia, Carrie J Lovitt, Prahlad V Raninga, Vicky M Avery, Giovanna Di Trapani, Kathryn F Tonissen
As essential elements of the tumor microenvironment, the variable oxygenation state of the tumor tissue, the extracellular matrix (ECM) and different cell types are important determinants of carcinogenesis. These elements may also influence how tumor cells respond to therapeutic treatments. In the present study, we assessed the anti-cancer activity of auranofin and its effect on the thioredoxin (Trx) system under conditions that closely resemble the in vivo tumor microenvironment with respect to the oxygen levels and tissue architecture...
October 2016: European Journal of Cell Biology
Genki Tanaka, Ken-Ichi Inoue, Takayuki Shimizu, Kazumi Akimoto, Keiichi Kubota
NRF2 stabilizes redox potential through genes for glutathione and thioredoxin antioxidant systems. Whether blockade of glutathione and thioredoxin is useful in eliminating cancer stem cells remain unknown. We used xenografts derived from colorectal carcinoma patients to investigate the pharmacological inhibition of glutathione and thioredoxin systems. Higher expression of five glutathione S-transferase isoforms (GSTA1, A2, M4, O2, and P1) was observed in xenograft-derived spheroids than in fibroblasts. Piperlongumine (2...
September 2016: Cancer Medicine
David Leitsch, Joachim Müller, Norbert Müller
The antioxidative enzyme thioredoxin reductase (TrxR) has been suggested to be a drug target in several pathogens, including the protist parasite Giardia lamblia. TrxR is also believed to catalyse the reduction of nitro drugs, e.g. metronidazole and furazolidone, a reaction required to render these compounds toxic to G. lamblia and other microaerophiles/anaerobes. It was the objective of this study to assess the potential of TrxR as a drug target in G. lamblia and to find direct evidence for the role of this enzyme in the activation of metronidazole and other nitro drugs...
July 22, 2016: International Journal for Parasitology, Drugs and Drug Resistance
Nelson S Torres, Johnathan J Abercrombie, Anand Srinivasan, Jose L Lopez-Ribot, Anand K Ramasubramanian, Kai P Leung
It is now well established that bacterial infections are often associated with biofilm phenotypes that demonstrate increased resistance to common antimicrobials. Further, due to the collective attrition of new antibiotic development programs by the pharmaceutical industries, drug repurposing is an attractive alternative. In this work, we screened 1,280 existing commercially available drugs in the Prestwick Chemical Library, some with previously unknown antimicrobial activity, against Staphylococcus aureus, one of the commonly encountered causative pathogens of burn and wound infections...
October 2016: Antimicrobial Agents and Chemotherapy
Joshua P Owings, Nina N McNair, Yiu Fung Mui, Tomas N Gustafsson, Arne Holmgren, Maria Contel, Joanna B Goldberg, Jan R Mead
Auranofin is an FDA-approved gold-containing compound used for the treatment of rheumatoid arthritis. Recent reports of antimicrobial activity against protozoa and bacteria indicate that auranofin targets the reductive enzyme thioredoxin reductase (TrxR). We evaluated auranofin as well as five auranofin analogs containing N-heterocyclic carbenes (instead of the triethylphosphane present in auranofin) and five gold-carbene controls for their ability to inhibit or kill Helicobacter pylori in vitro Auranofin completely inhibited bacterial growth at 1...
July 2016: FEMS Microbiology Letters
Nathan P Wiederhold, Thomas F Patterson, Anand Srinivasan, Ashok K Chaturvedi, Annette W Fothergill, Floyd L Wormley, Anand K Ramasubramanian, José L Lopez-Ribot
Repositioning old drugs can significantly decrease the time and effort that it takes to develop novel antifungal therapeutics, which represents a pressing and unmet clinical need due to the devastating nature of fungal infections. We have previously described the activity of auranofin, a gold thiol compound used to treat rheumatoid arthritis, against Candida albicans biofilms. Here we evaluate its antifungal spectrum of action and describe its activity against a variety of medically important fungi.
June 7, 2016: Virulence
Shaoruo Zhao, Haiyan Gong, Yongzhi Zhou, Houshuang Zhang, Jie Cao, Jinlin Zhou
Babesia microti is the primary causative agent of human babesiosis worldwide and associated with increased human health risks and the safety of blood supply. The parasite replicates in the host's red blood cells, thus, in order to counteract the oxidative stress and toxic effects, parasites employ a thioredoxin (Trx) system to maintain a redox balance. Since thioredoxin reductase (TrxR) plays a critical role in the system, in this study, we report the cloning, expression, and functional characterization of a novel TrxR from B...
August 2016: Parasitology Research
Chiara Nardon, Nicolò Pettenuzzo, Dolores Fregona
Gold has always aroused great interest in the history of mankind. It has been used for thousands of years for jewelry, religious cult valuables, durable goods and in the art world. However, few know that such a precious and noble metal was exploited in the past by the ancients also for its therapeutic properties. More recently, in the twentieth century some complexes containing gold centers in the oxidation state +1 were studied for the treatment of the rheumatoid arthritis and the orally-administered drug Auranofin was approved by the FDA in 1985...
May 3, 2016: Current Medicinal Chemistry
Jae-Chul Lee, Joon Ha Park, In Hye Kim, Geum-Sil Cho, Ji Hyeon Ahn, Hyun-Jin Tae, Soo Young Choi, Jun Hwi Cho, Dae Won Kim, Young-Guen Kwon, Il Jun Kang, Moo-Ho Won, Young-Myeong Kim
Preconditioning by brief ischemic episode induces tolerance to a subsequent lethal ischemic insult, and it has been suggested that reactive oxygen species are involved in this phenomenon. Thioredoxin 2 (Trx2), a small protein with redox-regulating function, shows cytoprotective roles against oxidative stress. Here, we had focused on the role of Trx2 in ischemic preconditioning (IPC)-mediated neuroprotection against oxidative stress followed by a subsequent lethal transient cerebral ischemia. Animals used in this study were randomly assigned to 6 groups; sham-operated group, ischemia-operated group, IPC plus (+) sham-operated group, IPC+ischemia-operated group, IPC+auranofin (a TrxR2 inhibitor)+sham-operated group and IPC+auranofin+ischemia-operated group...
April 26, 2016: Brain Pathology
Daniel Munro, Sheena Banh, Emianka Sotiri, Nahid Tamanna, Jason R Treberg
The most common methods of measuring mitochondrial hydrogen peroxide production are based on the extramitochondrial oxidation of a fluorescent probe such as amplex ultra red (AUR) by horseradish peroxidase (HRP). These traditional HRP-based assays only detect H2O2 that has escaped the matrix, raising the potential for substantial underestimation of production if H2O2 is consumed by matrix antioxidant pathways. To measure this underestimation, we characterized matrix consumers of H2O2 in rat skeletal muscle mitochondria, and developed specific means to inhibit these consumers...
July 2016: Free Radical Biology & Medicine
Qian Li, Stephanie B Wall, Changchun Ren, Markus Velten, Cynthia L Hill, Morgan L Locy, Lynette K Rogers, Trent E Tipple
Oxygen toxicity and antioxidant deficiencies contribute to the development of bronchopulmonary dysplasia. Aurothioglucose (ATG) and auranofin potently inhibit thioredoxin reductase-1 (TrxR1), and TrxR1 disruption activates nuclear factor E2-related factor 2 (Nrf2), a regulator of endogenous antioxidant responses. We have shown previously that ATG safely and effectively prevents lung injury in adult murine models, likely via Nrf2-dependent mechanisms. The current studies tested the hypothesis that ATG would attenuate hyperoxia-induced lung developmental deficits in newborn mice...
September 2016: American Journal of Respiratory Cell and Molecular Biology
H F Dos Santos, M A Vieira, G Y Sánchez Delgado, D Paschoal
The chemotherapy with gold complexes has been attempted since the 90s after the clinical success of auranofin, a gold(I) coordination complex. Currently, the organometallics compounds have shown promise in cancer therapy, mainly in those complexes containing N-heterocylic carbenes (NHC) as a ligand. The present study shows a kinetic analysis of the reaction of six alkyl-substituted NHC with cysteine (Cys), which is taken as an important bionucleophile representative. The first and second ligand exchange processes were analyzed with the complete description of the mechanism and energy profiles...
April 14, 2016: Journal of Physical Chemistry. A
Alessandra Folda, Anna Citta, Valeria Scalcon, Tito Calì, Francesco Zonta, Guido Scutari, Alberto Bindoli, Maria Pia Rigobello
The mitochondrial thioredoxin system (NADPH, thioredoxin reductase, thioredoxin) is a major redox regulator. Here we have investigated the redox correlation between this system and the mitochondrial enzyme cyclophilin D. The peptidyl prolyl cis-trans isomerase activity of cyclophilin D was stimulated by the thioredoxin system, while it was decreased by cyclosporin A and the thioredoxin reductase inhibitor auranofin. The redox state of cyclophilin D, thioredoxin 1 and 2 and peroxiredoxin 3 was measured in isolated rat heart mitochondria and in tumor cell lines (CEM-R and HeLa) by redox Western blot analysis upon inhibition of thioredoxin reductase with auranofin, arsenic trioxide, 1-chloro-2,4-dinitrobenzene or after treatment with hydrogen peroxide...
2016: Scientific Reports
Gayle M Gordillo, Ayan Biswas, Savita Khanna, James M Spieldenner, Xueliang Pan, Chandan K Sen
Endothelial cell tumors are the most common soft tissue tumors in infants. Tumor-forming endothelial (EOMA) cells are able to escape cell death fate despite excessive nuclear oxidant burden. Our previous work recognized perinuclear Nox-4 as a key contributor to EOMA growth. The objective of this work was to characterize the mechanisms by which EOMA cells evade oxidant toxicity and thrive. In EOMA cells, compared with in the cytosol, the nuclear GSSG/GSH ratio was 5-fold higher. Compared to the ratio observed in healthy murine aortic endothelial (MAE) cells, GSSG/GSH was over twice as high in EOMA cells...
May 6, 2016: Journal of Biological Chemistry
Mariana Fernandez-Caggiano, Ewald Schröder, Hyun-Ju Cho, Joseph Burgoyne, Javier Barallobre-Barreiro, Manuel Mayr, Philip Eaton
The role and responses of the dimeric DJ-1 protein to cardiac oxidative stress is incompletely understood. H2O2 induces a 50-kDa DJ-1 interprotein homodimer disulfide, known to form between Cys-53 on each subunit. A trimeric 75-kDa DJ-1 complex that mass spectrometry shows contained 2-Cys peroxiredoxin also formed and precedes the appearance of the disulfide dimer. These observations may represent peroxiredoxin sensing and transducing the oxidant signal to DJ-1. The dimeric disulfide DJ-1 complex was stabilized by auranofin, suggesting that thioredoxin recycles it in cells...
May 6, 2016: Journal of Biological Chemistry
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"