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Cancer AND NadPH

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https://www.readbyqxmd.com/read/28723216/lycopene-inhibits-human-liver-adenocarcinoma-sk-hep-1-cells-metastasis-by-down-regulation-of-nadph-oxidase-4-protein-expression
#1
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 to disrupt 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 highest inhibition of 64...
July 19, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28709950/characterization-of-potent-and-selective-iodonium-class-inhibitors-of-nadph-oxidases
#2
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
#3
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
#4
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
#5
Kai Zheng, Yingchun Jiang, Chenghui Liao, Xiaopeng Hu, Yan Li, Yong Zeng, Jian Zhang, Xuli Wu, Haiqiang Wu, Lizhong Liu, Yifei Wang, Zhendan He
Tumor cells frequently obtain their chemoresistance through deregulating apoptotic signaling and activating protective autophagy. Therefore, exploring efficient chemotherapeutic agents or isolating novel natural products that can trigger non-apoptotic and non-autophagic cell death such as lysosome-associated death is emergently required. We have recently shown that Gypenoside L (Gyp-L), a saponin isolated from Gynostemma pentaphyllum, induces lysosome swelling and cell death in esophageal cancer cells. However, contributions of vacuolization and lysosome to cell death remain unclear...
July 11, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28692052/disrupting-g6pd-mediated-redox-homeostasis-enhances-chemosensitivity-in-colorectal-cancer
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28649560/escaping-death-mitochondrial-redox-homeostasis-in-cancer-cells
#10
REVIEW
Francesco Ciccarese, Vincenzo Ciminale
Reactive oxygen species (ROS) are important signaling molecules that act through the oxidation of nucleic acids, proteins, and lipids. Several hallmarks of cancer, including uncontrolled proliferation, angiogenesis, and genomic instability, are promoted by the increased ROS levels commonly found in tumor cells. To counteract excessive ROS accumulation, oxidative stress, and death, cancer cells tightly regulate ROS levels by enhancing scavenging enzymes, which are dependent on the reducing cofactor nicotinamide adenine dinucleotide phosphate (NADPH)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28626501/nadph-oxidases-insights-into-selected-functions-and-mechanisms-of-action-in-cancer-and-stem-cells
#11
REVIEW
Magdalena Skonieczna, Tomasz Hejmo, Aleksandra Poterala-Hejmo, Artur Cieslar-Pobuda, Rafal J Buldak
NADPH oxidases (NOX) are reactive oxygen species- (ROS-) generating enzymes regulating numerous redox-dependent signaling pathways. NOX are important regulators of cell differentiation, growth, and proliferation and of mechanisms, important for a wide range of processes from embryonic development, through tissue regeneration to the development and spread of cancer. In this review, we discuss the roles of NOX and NOX-derived ROS in the functioning of stem cells and cancer stem cells and in selected aspects of cancer cell physiology...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28620580/the-human-nadph-oxidase-nox4-regulates-cytoskeletal-organization-in-two-cancer-cell-lines-hepg2-and-sh-sy5y
#12
Simon Auer, Mark Rinnerthaler, Johannes Bischof, Maria Karolin Streubel, Hannelore Breitenbach-Koller, Roland Geisberger, Elmar Aigner, Janne Cadamuro, Klaus Richter, Mentor Sopjani, Elisabeth Haschke-Becher, Thomas Klaus Felder, Michael Breitenbach
NADPH oxidases of human cells are not only functional in defense against invading microorganisms and for oxidative reactions needed for specialized biosynthetic pathways but also during the past few years have been established as signaling modules. It has been shown that human Nox4 is expressed in most somatic cell types and produces hydrogen peroxide, which signals to remodel the actin cytoskeleton. This correlates well with the function of Yno1, the only NADPH oxidase of yeast cells. Using two established tumor cell lines, which are derived from hepatic and neuroblastoma tumors, respectively, we are showing here that in both tumor models Nox4 is expressed in the ER (like the yeast NADPH oxidase), where according to published literature, it produces hydrogen peroxide...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28607489/the-metabolic-function-of-cyclin-d3-cdk6-kinase-in-cancer-cell-survival
#13
Haizhen Wang, Brandon N Nicolay, Joel M Chick, Xueliang Gao, Yan Geng, Hong Ren, Hui Gao, Guizhi Yang, Juliet A Williams, Jan M Suski, Mark A Keibler, Ewa Sicinska, Ulrike Gerdemann, W Nicholas Haining, Thomas M Roberts, Kornelia Polyak, Steven P Gygi, Nicholas J Dyson, Piotr Sicinski
D-type cyclins (D1, D2 and D3) and their associated cyclin-dependent kinases (CDK4 and CDK6) are components of the core cell cycle machinery that drives cell proliferation. Inhibitors of CDK4 and CDK6 are currently being tested in clinical trials for patients with several cancer types, with promising results. Here, using human cancer cells and patient-derived xenografts in mice, we show that the cyclin D3-CDK6 kinase phosphorylates and inhibits the catalytic activity of two key enzymes in the glycolytic pathway, 6-phosphofructokinase and pyruvate kinase M2...
June 15, 2017: Nature
https://www.readbyqxmd.com/read/28584401/chemopreventive-effects-of-a-low-side-effect-antibiotic-drug-erythromycin-on-mouse-intestinal-tumors
#14
Takahiro Hamoya, Shingo Miyamoto, Susumu Tomono, Gen Fujii, Ruri Nakanishi, Masami Komiya, Shuya Tamura, Kyoko Fujimoto, Jiro Toshima, Keiji Wakabayashi, Michihiro Mutoh
It is important to establish effective methods for preventing colorectal cancer because the number of colorectal cancer deaths is increasing. Erythromycin one of the macrolide antibiotics, has been shown to exert pleiotropic effects, such as anti-inflammatory and anti-oxidative effects, on mammalian cells. In the present study, we aimed to evaluate the preventive effects of erythromycin on intestinal carcinogenesis. We first confirmed that erythromycin suppresses the transcriptional activity of nuclear factor-κB and activator protein-1 and the expression of its downstream targets, interleukin-6 and cyclooxygenase-2 in human colon cancer cells...
May 2017: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/28578276/decoding-nadph-oxidase-4-expression-in-human-tumors
#15
Jennifer L Meitzler, Hala R Makhlouf, Smitha Antony, Yongzhong Wu, Donna Butcher, Guojian Jiang, Agnes Juhasz, Jiamo Lu, Iris Dahan, Pidder Jansen-Dürr, Haymo Pircher, Ajay M Shah, Krishnendu Roy, James H Doroshow
NADPH oxidase 4 (NOX4) is a redox active, membrane-associated protein that contributes to genomic instability, redox signaling, and radiation sensitivity in human cancers based on its capacity to generate H2O2 constitutively. Most studies of NOX4 in malignancy have focused on the evaluation of a small number of tumor cell lines and not on human tumor specimens themselves; furthermore, these studies have often employed immunological tools that have not been well characterized. To determine the prevalence of NOX4 expression across a broad range of solid tumors, we developed a novel monoclonal antibody that recognizes a specific extracellular region of the human NOX4 protein, and that does not cross-react with any of the other six members of the NOX gene family...
May 26, 2017: Redox Biology
https://www.readbyqxmd.com/read/28578013/paradoxical-roles-of-dual-oxidases-in-cancer-biology
#16
REVIEW
Andrew C Little, Arvis Sulovari, Karamatullah Danyal, David E Heppner, David J Seward, Albert van der Vliet
Dysregulated oxidative metabolism is a well-recognized aspect of cancer biology, and many therapeutic strategies are based on targeting cancers by altering cellular redox pathways. The NADPH oxidases (NOXes) present an important enzymatic source of biological oxidants, and the expression and activation of several NOX isoforms are frequently dysregulated in many cancers. Cell-based studies have demonstrated a role for several NOX isozymes in controlling cell proliferation and/or cell migration, further supporting a potential contributing role for NOX in promoting cancer...
May 31, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28574838/histone-modifications-affect-differential-regulation-of-tgf%C3%AE-induced-nadph-oxidase-4-nox4-by-wild-type-and-mutant-p53
#17
Howard E Boudreau, Wei Feng Ma, Agnieszka Korzeniowska, Jonathan J Park, Medha A Bhagwat, Thomas L Leto
Previously, we showed wild-type (WT) and mutant (mut) p53 differentially regulate reactive oxygen species (ROS) generation by NADPH oxidase-4 (NOX4): p53-WT suppresses TGFβ-induced NOX4, ROS and cell migration, whereas tumor-associated mut-p53 proteins enhance NOX4 expression and cell migration. Here, we extended our findings on the effects of p53 on NOX4 in several tumors and examined the basis of NOX4 transcriptional regulation by p53 and SMAD3. Statistical analysis of expression data from primary tumors available from The Cancer Genome Atlas (TCGA) detected correlations between mut-p53 and increased NOX4 expression...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28574504/nox2-dependent-atm-kinase-activation-dictates-pro-inflammatory-macrophage-phenotype-and-improves-effectiveness-to-radiation-therapy
#18
Qiuji Wu, Awatef Allouch, Audrey Paoletti, Celine Leteur, Celine Mirjolet, Isabelle Martins, Laurent Voisin, Frédéric Law, Haithem Dakhli, Elodie Mintet, Maxime Thoreau, Zeinaf Muradova, Mélanie Gauthier, Olivier Caron, Fabien Milliat, David M Ojcius, Filippo Rosselli, Eric Solary, Nazanine Modjtahedi, Eric Deutsch, Jean-Luc Perfettini
Although tumor-associated macrophages have been extensively studied in the control of response to radiotherapy, the molecular mechanisms involved in the ionizing radiation-mediated activation of macrophages remain elusive. Here we show that ionizing radiation induces the expression of interferon regulatory factor 5 (IRF5) promoting thus macrophage activation toward a pro-inflammatory phenotype. We reveal that the activation of the ataxia telangiectasia mutated (ATM) kinase is required for ionizing radiation-elicited macrophage activation, but also for macrophage reprogramming after treatments with γ-interferon, lipopolysaccharide or chemotherapeutic agent (such as cisplatin), underscoring the fact that the kinase ATM plays a central role during macrophage phenotypic switching toward a pro-inflammatory phenotype through the regulation of mRNA level and post-translational modifications of IRF5...
June 2, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28564604/cancer-associated-idh1-promotes-growth-and-resistance-to-targeted-therapies-in-the-absence-of-mutation
#19
Andrea E Calvert, Alexandra Chalastanis, Yongfei Wu, Lisa A Hurley, Fotini M Kouri, Yingtao Bi, Maureen Kachman, Jasmine L May, Elizabeth Bartom, Youjia Hua, Rama K Mishra, Gary E Schiltz, Oleksii Dubrovskyi, Andrew P Mazar, Marcus E Peter, Hongwu Zheng, C David James, Charles F Burant, Navdeep S Chandel, Ramana V Davuluri, Craig Horbinski, Alexander H Stegh
Oncogenic mutations in two isocitrate dehydrogenase (IDH)-encoding genes (IDH1 and IDH2) have been identified in acute myelogenous leukemia, low-grade glioma, and secondary glioblastoma (GBM). Our in silico and wet-bench analyses indicate that non-mutated IDH1 mRNA and protein are commonly overexpressed in primary GBMs. We show that genetic and pharmacologic inactivation of IDH1 decreases GBM cell growth, promotes a more differentiated tumor cell state, increases apoptosis in response to targeted therapies, and prolongs the survival of animal subjects bearing patient-derived xenografts (PDXs)...
May 30, 2017: Cell Reports
https://www.readbyqxmd.com/read/28554049/increased-susceptibility-of-idh2-deficient-mice-to-dextran-sodium-sulfate-induced-colitis
#20
Hanvit Cha, Seoyoon Lee, Sung Hwan Kim, Hyunjin Kim, Dong-Seok Lee, Hyun-Shik Lee, Jin Hyup Lee, Jeen-Woo Park
Inflammatory bowel disease (IBD) is a group of chronic, relapsing, immunological, inflammatory disorders of the gastrointestinal tract including ulcerative colitis (UC) and Crohn's disease (CD). It has been reported that UC, which is studied using a dextran sodium sulfate (DSS)-induced colitis model, is associated with the production of reactive oxygen species (ROS) and the apoptosis of intestine epithelial cells (IEC). Mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2) has been reported as an essential enzyme in the mitochondrial antioxidant system via generation of NADPH...
May 20, 2017: Redox Biology
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