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Cancer AND NadPH

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https://www.readbyqxmd.com/read/28793782/direct-activation-of-nadph-oxidase-2-by-2-deoxyribose-1-phosphate-triggers-nuclear-factor-kappa-b-dependent-angiogenesis
#1
Dina Vara, Joanna M Watt, Tiago M Fortunato, Harry Mellor, Matthew Burgess, Kate Wicks, Kimberly Mace, Shaun Reeksting, Anneke T Lubben, Caroline Pd Wheeler-Jones, Giordano Pula
AIMS: Deoxyribose-1-phosphate (dRP) is a pro-angiogenic paracrine stimulus released by cancer cells, platelets and macrophages and acting on endothelial cells. The objective of this study was to clarify how dRP stimulates angiogenic responses in human endothelial cells. RESULTS: Live cell imaging, electron paramagnetic resonance (EPR), pull-down of dRP-interacting proteins followed by immunoblotting, gene silencing of different NOXs and their regulatory co-subunits by siRNA transfection, and experiments with inhibitors of the sugar transporter GLUT1 were utilized to demonstrate that dRP acts intracellularly by directly activating the endothelial NADPH oxidase 2 (NOX2) complex, but not NOX4...
August 10, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28762750/genome-scale-modeling-of-nadph-driven-%C3%AE-lapachone-sensitization-in-head-and-neck-squamous-cell-carcinoma
#2
Joshua E Lewis, Francesco Costantini, Jade Mims, Xiaofei Chen, Cristina Furdui, David A Boothman, Melissa L Kemp
AIMS: The purpose of this study was to investigate differential NADPH production between radiation-sensitive and -resistant head and neck squamous cell carcinoma (HNSCC) cell lines, and whether these differences are predictive of sensitivity to the chemotherapeutic ß-lapachone. RESULTS: We have developed a novel human genome-scale metabolic modeling platform that combines transcriptomic, kinetic, thermodynamic, and metabolite concentration data. Upon incorporation of this information into cell-line specific models, we observed that the radiation-resistant HNSCC model redistributed flux through several major NADPH producing reactions...
August 1, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28762556/nadph-oxidase-5-nox5-induced-reactive-oxygen-signaling-modulates-normoxic-hif-1%C3%AE-and-p27-kip1-expression-in-malignant-melanoma-and-other-human-tumors
#3
Smitha Antony, Guojian Jiang, Yongzhong Wu, Jennifer L Meitzler, Hala R Makhlouf, Diana C Haines, Donna Butcher, Dave S Hoon, Jiuping Ji, Yiping Zhang, Agnes Juhasz, Jiamo Lu, Han Liu, Iris Dahan, Mariam Konate, Krishnendu K Roy, James H Doroshow
NADPH oxidase 5 (NOX5) generated reactive oxygen species (ROS) have been implicated in signaling cascades that regulate cancer cell proliferation. To evaluate and validate NOX5 expression in human tumors, we screened a broad range of tissue microarrays (TMAs), and report substantial overexpression of NOX5 in malignant melanoma and cancers of the prostate, breast, and ovary. In human UACC-257 melanoma cells that possesses high levels of functional endogenous NOX5, overexpression of NOX5 resulted in enhanced cell growth, increased numbers of BrdU positive cells, and increased γ-H2AX levels...
August 1, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28761052/uchl1-hif-1-axis-mediated-antioxidant-property-of-cancer-cells-as-a-therapeutic-target-for-radiosensitization
#4
Ryota Nakashima, Yoko Goto, Sho Koyasu, Minoru Kobayashi, Akiyo Morinibu, Michio Yoshimura, Masahiro Hiraoka, Ester M Hammond, Hiroshi Harada
Hypoxia-inducible factor 1 (HIF-1) has been recognized as an important mediator of the reprogramming of carbohydrate metabolic pathways from oxidative phosphorylation to accelerated glycolysis. Although this reprogramming has been associated with the antioxidant and radioresistant properties of cancer cells, gene networks triggering the HIF-1-mediated reprogramming and molecular mechanisms linking the reprogramming with radioresistance remain to be determined. Here, we show that Ubiquitin C-terminal hydrolase-L1 (UCHL1), which we previously identified as a novel HIF-1 activator, increased the radioresistance of cancer cells by producing an antioxidant, reduced glutathione (GSH), through HIF-1-mediated metabolic reprogramming...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28757135/synergism-between-thioredoxin-reductase-inhibitor-ethaselen-and-sodium-selenite-in-inhibiting-proliferation-and-inducing-death-of-human-non-small-cell-lung-cancer-cells
#5
Xiaoqing Zheng, Wei Xu, Ruoxuan Sun, Hanwei Yin, Chaoran Dong, Huihui Zeng
New effective treatment for human non-small cell lung cancer (NSCLC) is needed. The thioredoxin (Trx) system composes of thioredoxin reductase (TrxR), Trx and NADPH. In this study, we combined an organic selenium compound--TrxR inhibitor ethaselen (BBSKE) with low dosage sodium selenite to inhibit proliferation and induce death of NSCLC cells, and identified underlying mechanisms. Synergistic anti-proliferation effect of BBSKE and selenite was found in human NSCLC cell lines, A549, NCI-H1299 and NCI-1266. A significant increase of apoptosis, necrosis and autophagy were observed in the group of BBSKE plus selenite in A549 cells...
July 27, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28756208/activation-of-aldh1a1-in-mda-mb-468-breast-cancer-cells-that-over-express-cyp2j2-protects-against-paclitaxel-dependent-cell-death-mediated-by-reactive-oxygen-species
#6
Sarah E Allison, Yongjuan Chen, Nenad Petrovic, Jian Zhang, Kirsi Bourget, Peter I Mackenzie, Michael Murray
Cytochrome P450 2J2 (CYP2J2) expression is elevated in breast and other tumours, and is known to be protective against cytotoxic agents that may be used in cancer chemotherapy. This study evaluated the mechanisms by which MDA-MB-468 breast cancer cells that stably expressed CYP2J2 (MDA-2J2 cells) were protected against killing by the anti-cancer agent paclitaxel. Compared to control cells caspase-3/7 activation by paclitaxel was lower in MDA-2J2 cells, while cell proliferation and colony formation following paclitaxel treatment were increased...
July 27, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28751891/deconvolution-of-the-response-to-bacillus-calmette-gu%C3%A3-rin-reveals-nf-%C3%AE%C2%BAb-induced-cytokines-as-autocrine-mediators-of-innate-immunity
#7
Aurélie Bisiaux, Jeremy Boussier, Darragh Duffy, Lluis Quintana-Murci, Magnus Fontes, Matthew L Albert
Bacillus Calmette-Guérin (BCG) is used as a vaccine and diagnostic test for tuberculosis, as well as immunotherapy in the treatment of bladder cancer. While clinically useful, the response to mycobacterial stimulation is complex and the induced protein signature remains poorly defined. We characterized the cell types directly engaged by BCG, as well as the induced cytokine loops that transmit signal(s) to bystander cells. Standardized whole-blood stimulations and mechanistic studies on single and purified cell populations identified distinct patterns of activation in monocytes as compared to neutrophils and invariant lymphocyte populations...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28744338/role-of-kallistatin-treatment-in-aging-and-cancer-by-modulating-mir-34a-and-mir-21-expression
#8
REVIEW
Julie Chao, Youming Guo, Pengfei Li, Lee Chao
Kallistatin is an endogenous protein that regulates differential signaling pathways and a wide spectrum of biological activities via its two structural elements: an active site and a heparin-binding domain. Kallistatin via its heparin-binding site inhibits vascular inflammation and oxidative stress by antagonizing TNF-α-induced NADPH oxidase activity, NF-κB activation, and inflammatory gene expression in endothelial cells. Moreover, kallistatin via its active site inhibits microRNA-34a (miR-34a) synthesis and stimulates eNOS and SIRT1 expression in endothelial progenitor cells, whereas its heparin-binding site is crucial for blocking TNF-α-induced miR-21 expression and oxidative stress, thus reducing cellular senescence...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28739529/control-of-the-nadph-supply-for-oxidative-stress-handling-in-cancer-cells
#9
Rafael Moreno-Sánchez, Juan Carlos Gallardo-Pérez, Sara Rodríguez-Enríquez, Emma Saavedra, Álvaro Marín-Hernández
It has not been systematically analyzed whether the NADPH supply is a limiting factor for oxidative stress management in cancer cells. In the present work, it was determined in non-cancer and cancer cells the protein contents and kinetomics of (i) the cytosolic enzymes responsible for the NADPH production (i.e., Glc6PDH, 6PGDH, ME, IDH-1); and (ii) the two main enzymes responsible for NADPH/NADP(+) and GSH/GSSG recycling (GR, GPx-1) associated to oxidative stress management. With these data, kinetic models were built and further validated...
July 21, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28738532/genipin-attenuates-cisplatin-induced-nephrotoxicity-by-counteracting-oxidative-stress-inflammation-and-apoptosis
#10
Eglal Mahgoub, Shanmugam Muthu Kumaraswamy, Kamal Hassan Kader, Balaji Venkataraman, Shreesh Ojha, Ernest Adeghate, Mohanraj Rajesh
Cisplatin (CP) is a potent and widely used chemotherapeutic agent. However, the clinical benefits of CP are compromised because it elicits nephrotoxicity and ototoxicity. In this study, we investigated the nephroprotective effects of the phytochemical genipin (GP) isolated from the gardenia (Gardenia jasminoides) fruit, using a murine model of CP-induced nephropathy. GP pretreatment attenuated the CP-induced renal tissue injury by diminishing the serum blood urea nitrogen, creatinine, and cystatin C levels, as well as those of kidney injury molecule-1...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28733324/nadph-oxidase-2-derived-superoxide-drives-mitochondrial-transfer-from-bone-marrow-stromal-cells-to-leukemic-blasts
#11
Christopher R Marlein, Lyubov Zaitseva, Rachel E Piddock, Stephen Robinson, Dylan Edwards, Manar S Shafat, Zhigang Zhou, Matthew Lawes, Kristian M Bowles, Stuart A Rushworth
Improvements in the understanding of the metabolic cross-talk between cancer and its micro-environment are expected to lead to novel therapeutic approaches. Acute myeloid leukemia (AML) cells have increased mitochondria compared to non-malignant CD34+ hematopoietic progenitor cells. Furthermore, contrary to the Warburg hypothesis, (AML) relies on oxidative phosphorylation to generate ATP. Here we report that in human AML, NOX2 generates superoxide which stimulates bone marrow stromal cells (BMSC) to AML blast transfer of mitochondria through AML derived tunnelling nanotubes...
July 21, 2017: Blood
https://www.readbyqxmd.com/read/28723216/lycopene-inhibits-metastasis-of-human-liver-adenocarcinoma-sk-hep-1-cells-by-downregulation-of-nadph-oxidase-4-protein-expression
#12
Bo-Yi Jhou, Tuzz-Ying Song, Inn Lee, Miao-Lin Hu, Nae-Cherng Yang
NADPH oxidase 4 (NOX4), with the sole function to produce reactive oxygen species (ROS), can be a molecular target for disrupting cancer metastasis. Several studies have indicated that lycopene exhibited anti-metastatic actions in vitro and in vivo. However, the role of NOX4 in the anti-metastatic action of lycopene remains unknown. Herein, we first confirmed the anti-metastatic effect of lycopene (0.1-5 μM) on human liver adenocarcinoma SK-Hep-1 cells. We showed that lycopene significantly inhibited NOX4 protein expression, with the strongest inhibition of 64...
August 16, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28709950/characterization-of-potent-and-selective-iodonium-class-inhibitors-of-nadph-oxidases
#13
Jiamo Lu, Prabhakar Risbood, Charles T Kane, Md Tafazzal Hossain, Larry Anderson, Kimberly Hill, Anne Monks, Yongzhong Wu, Smitha Antony, Agnes Juhasz, Han Liu, Guojian Jiang, Erik Harris, Krishnendu Roy, Jennifer L Meitzler, Mariam Konaté, James H Doroshow
The NADPH oxidases (NOXs) play a recognized role in the development and progression of inflammation-associated disorders, as well as cancer. To date, several NOX inhibitors have been developed, through either high throughput screening or targeted disruption of NOX interaction partners, although only a few have reached clinical trials. To improve the efficacy and bioavailability of the iodonium class NOX inhibitor diphenylene iodonium (DPI), we synthesized 36 analogs of DPI, focusing on improved solubility and functionalization...
July 11, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28705010/isocitrate-dehydrogenase-mutation-as-a-therapeutic-target-in-gliomas
#14
Catherine H Han, Tracy T Batchelor
Isocitrate dehydrogenases (IDH) are important enzymes that catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG), producing NADPH in the process. More than 80% of low-grade gliomas and secondary glioblastoma (GBM) harbor an IDH mutation. IDH mutations involve the catalytic pocket of the enzyme and lead to a neomorphic ability to produce 2-hydroxyglutarate (2HG) while oxidizing NADPH to NADP+. 2HG is considered as an 'oncometabolite' which is thought to be responsible for many, if not all, biologic effects of IDH mutations...
June 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28698499/molecular-mechanisms-behind-free-radical-scavengers-function-against-oxidative-stress
#15
REVIEW
Fereshteh Ahmadinejad, Simon Geir Møller, Morteza Hashemzadeh-Chaleshtori, Gholamreza Bidkhori, Mohammad-Saeid Jami
Accumulating evidence shows that oxidative stress is involved in a wide variety of human diseases: rheumatoid arthritis, Alzheimer's disease, Parkinson's disease, cancers, etc. Here, we discuss the significance of oxidative conditions in different disease, with the focus on neurodegenerative disease including Parkinson's disease, which is mainly caused by oxidative stress. Reactive oxygen and nitrogen species (ROS and RNS, respectively), collectively known as RONS, are produced by cellular enzymes such as myeloperoxidase, NADPH-oxidase (nicotinamide adenine dinucleotide phosphate-oxidase) and nitric oxide synthase (NOS)...
July 10, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28697598/nox2-mediated-tfeb-activation-and-vacuolization-regulate-lysosome-associated-cell-death-induced-by-gypenoside-l-a-saponin-isolated-from-gynostemma-pentaphyllum
#16
Kai Zheng, Yingchun Jiang, Chenghui Liao, Xiaopeng Hu, Yan Li, Yong Zeng, Jian Zhang, Xuli Wu, Haiqiang Wu, Lizhong Liu, Yifei Wang, Zhendan He
Downregulation of apoptotic signal pathway and activation of protective autophagy mainly contribute to the chemoresistance of tumor cells. Therefore, exploring efficient chemotherapeutic agents or isolating novel natural products that can trigger nonapoptotic and nonautophagic cell death such as lysosome-associated death is emergently required. We have recently extracted a saponin, gypenoside L (Gyp-L), from Gynostemma pentaphyllum and showed that Gyp-L was able to induce nonapoptotic cell death of esophageal cancer cells associated with lysosome swelling...
August 9, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28692052/disrupting-g6pd-mediated-redox-homeostasis-enhances-chemosensitivity-in-colorectal-cancer
#17
H-Q Ju, Y-X Lu, Q-N Wu, J Liu, Z-L Zeng, H-Y Mo, Y Chen, T Tian, Y Wang, T-B Kang, D Xie, M-S Zeng, P Huang, R-H Xu
Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme that generates NADPH to maintain reduced glutathione (GSH), which scavenges reactive oxygen species (ROS) to protect cancer cell from oxidative damage. In this study, we mainly investigate the potential roles of G6PD in colorectal cancer (CRC) development and chemoresistance. We discover that G6PD is overexpressed in CRC cells and patient specimens. High expression of G6PD predicts poor prognosis and correlated with poor outcome of oxaliplatin-based first-line chemotherapy in patients with CRC...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28660426/recent-developments-in-the-probes-and-assays-for-measurement-of-the-activity-of-nadph-oxidases
#18
Jacek Zielonka, Micael Hardy, Radosław Michalski, Adam Sikora, Monika Zielonka, Gang Cheng, Olivier Ouari, Radosław Podsiadły, Balaraman Kalyanaraman
NADPH oxidases are a family of enzymes capable of transferring electrons from NADPH to molecular oxygen. A major function of NADPH oxidases is the activation of molecular oxygen into reactive oxygen species. Increased activity of NADPH oxidases has been implicated in various pathologies, including cardiovascular disease, neurological dysfunction, and cancer. Thus, NADPH oxidases have been identified as a viable target for the development of novel therapeutics exhibiting inhibitory effects on NADPH oxidases...
June 29, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28658624/hepatocyte-hyperproliferation-upon-liver-specific-co-disruption-of-thioredoxin-1-thioredoxin-reductase-1-and-glutathione-reductase
#19
Justin R Prigge, Lucia Coppo, Sebastin S Martin, Fernando Ogata, Colin G Miller, Michael D Bruschwein, David J Orlicky, Colin T Shearn, Jean A Kundert, Julia Lytchier, Alix E Herr, Åse Mattsson, Matthew P Taylor, Tomas N Gustafsson, Elias S J Arnér, Arne Holmgren, Edward E Schmidt
Energetic nutrients are oxidized to sustain high intracellular NADPH/NADP(+) ratios. NADPH-dependent reduction of thioredoxin-1 (Trx1) disulfide and glutathione disulfide by thioredoxin reductase-1 (TrxR1) and glutathione reductase (Gsr), respectively, fuels antioxidant systems and deoxyribonucleotide synthesis. Mouse livers lacking both TrxR1 and Gsr sustain these essential activities using an NADPH-independent methionine-consuming pathway; however, it remains unclear how this reducing power is distributed...
June 27, 2017: Cell Reports
https://www.readbyqxmd.com/read/28653623/replication-study-the-common-feature-of-leukemia-associated-idh1-and-idh2-mutations-is-a-neomorphic-enzyme-activity-converting-alpha-ketoglutarate-to-2-hydroxyglutarate
#20
Megan Reed Showalter, Jason Hatakeyama, Tomas Cajka, Kacey VanderVorst, Kermit L Carraway, Oliver Fiehn
In 2016, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Fiehn et al., 2016), that described how we intended to replicate selected experiments from the paper "The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate" (Ward et al., 2010). Here, we report the results of those experiments. We found that cells expressing R172K mutant IDH2 did not display isocitrate-dependent NADPH production above vector control levels, in contrast to the increased production observed with wild-type IDH2...
June 27, 2017: ELife
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