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NAD+ AND cancer

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https://www.readbyqxmd.com/read/28208702/the-glutamate-dehydrogenase-pathway-and-its-roles-in-cell-and-tissue-biology-in-health-and-disease
#1
REVIEW
Andreas Plaitakis, Ester Kalef-Ezra, Dimitra Kotzamani, Ioannis Zaganas, Cleanthe Spanaki
Glutamate dehydrogenase (GDH) is a hexameric enzyme that catalyzes the reversible conversion of glutamate to α-ketoglutarate and ammonia while reducing NAD(P)⁺ to NAD(P)H. It is found in all living organisms serving both catabolic and anabolic reactions. In mammalian tissues, oxidative deamination of glutamate via GDH generates α-ketoglutarate, which is metabolized by the Krebs cycle, leading to the synthesis of ATP. In addition, the GDH pathway is linked to diverse cellular processes, including ammonia metabolism, acid-base equilibrium, redox homeostasis (via formation of fumarate), lipid biosynthesis (via oxidative generation of citrate), and lactate production...
February 8, 2017: Biology
https://www.readbyqxmd.com/read/28203294/correlation-between-nad-p-h-quinone-oxidoreductase-1-c609t-polymorphism-and-increased-risk-of-esophageal-cancer-evidence-from-a-meta-analysis
#2
Jingfang Diao, Jie Bao, Jianxin Peng, Jiaqiang Mo, Qing Ye, Junming He
NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T gene polymorphisms have been reported to influence the risk for esophageal cancer (EC) in many studies. However, the results remain controversial and ambiguous. We performed a meta-analysis, which included 13 independent studies with a total of 2357 subjects, to examine the association between NQO1 C609T polymorphism and EC. The association was assessed by five different gene models. The overall analysis suggested that the variant allele and genotypes were significantly related to increased risk of EC (odds ratio [OR] T versus C = 1...
January 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28191864/overexpression-of-nad-p-h-quinone-oxidoreductase-1-inhibits-hepatocellular-carcinoma-cell-proliferation-and-induced-apoptosis-by-activating-ampk-pgc-1%C3%AE-pathway
#3
Xin Zhang, Kun Han, Dong-Hong Yuan, Cun-Ying Meng
Hepatocellular carcinoma (HCC) is the most common lethal malignancy and a leading cause of malignancy-associated death in many countries, but mainly in Asia. Expression of the NAD(P)H:quinone oxidoreductase 1 (NQO1) protein is involved in the growth of various human cancers, including HCC. NQO1 is considered an inhibitor of cancers. The present study aimed to investigate the function and mechanism of NQO1 in HCC. In this study, we found that NQO1 overexpression decreased HCC cell SK-hep-1 and Hep3B cell proliferation and induced apoptosis...
February 13, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28165742/identification-of-novel-triazole-based-nicotinamide-phosphoribosyltransferase-nampt-inhibitors-endowed-with-anti-proliferative-and-anti-inflammatory-activity
#4
Cristina Travelli, Silvio Aprile, Reza Rahimian, Ambra A Grolla, Federica Rogati, Mattia Bertolotti, Floriana Malagnino, Rosanna Di Paola, Daniela Impellizzeri, Roberta Fusco, Valentina Mercalli, Alberto Massarotti, Giorgio Stortini, Salvatore Terrazzino, Erika Del Grosso, Gohar Fakhfouri, Maria Pia Troiani, Maria Alessandra Alisi, Giorgio Grosa, Giovanni Sorba, Pier Luigi Canonico, Giuseppe Orsomando, Salvatore Cuzzocrea, Armando A Genazzani, Ubaldina Galli, Gian Cesare Tron
Nicotinamide phosphoribosyltransferase (NAMPT) is a key enzyme involved in the recycling of nicotinamide to maintain adequate NAD levels inside the cells. It has been postulated to be a pharmacological target as it is over-expressed in cancer cells as well as in inflammatory diseases. We describe the synthesis and characterization of a novel class of one-digit nanomolar NAMPT inhibitors based on in vitro characterization. The most active compound tested, 30c, displayed activity in a xenograft and in allograft models, strengthening the potential of NAMPT inhibitors as anti-tumoural drugs...
February 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28164517/prognostic-and-predictive-role-of-sirtuin1-expression-in-lung-adenocarcinoma
#5
Jun Wang, Changli Wang
BACKGROUND: SIRT1 is the homologue of sir2 in mammals, which is a nicotinamide adenine dinucleotide (NAD+) dependent histone deacetylase. Several studies have reported that the overexpression of Sirtuin1 (SIRT1) was associated with poor prognosis in various human cancers. However, little is known regarding the prognostic value of SIRT1 in lung adenocarcinoma. METHODS: SIRT 1 expression in tissues of 60 lung adenocarcinoma (LAC) patients was evaluated using immunohistochemistry...
October 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28162896/haploinsufficiency-of-sirt1-enhances-glutamine-metabolism-and-promotes-cancer-development
#6
Natalie S X Ren, Ming Ji, Erik J Tokar, Evan L Busch, Xiaojiang Xu, DeAsia Lewis, Xiangchun Li, Aiwen Jin, Yanping Zhang, William K K Wu, Weichun Huang, Leping Li, David C Fargo, Temitope O Keku, Robert S Sandler, Xiaoling Li
SIRT1, the most conserved mammalian NAD(+)-dependent protein deacetylase, plays a vital role in the regulation of metabolism, stress responses, and genome stability. However, the role of SIRT1 in the multi-step process leading to transformation and/or tumorigenesis, as either a tumor suppressor or tumor promoter, is complex and may be dependent upon the context in which SIRT1 activity is altered, and the role of SIRT1 in tumor metabolism is unknown. Here, we demonstrate that SIRT1 dose-dependently regulates cellular glutamine metabolism and apoptosis, which in turn differentially impact cell proliferation and cancer development...
January 31, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28160567/ews-fli1-confers-exquisite-sensitivity-to-nampt-inhibition-in-ewing-sarcoma-cells
#7
Cornelia N Mutz, Raphaela Schwentner, Dave N T Aryee, Eric D J Bouchard, Edgard M Mejia, Grant M Hatch, Maximilian O Kauer, Anna M Katschnig, Jozef Ban, Antje Garten, Javier Alonso, Versha Banerji, Heinrich Kovar
Ewing sarcoma (EwS) is the second most common bone cancer in children and adolescents with a high metastatic potential. EwS development is driven by a specific chromosomal translocation resulting in the generation of a chimeric EWS-ETS transcription factor, most frequently EWS-FLI1.Nicotinamide adenine dinucleotide (NAD) is a key metabolite of energy metabolism involved in cellular redox reactions, DNA repair, and in the maintenance of genomic stability. This study describes targeting nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of NAD synthesis, by FK866 in EwS cells...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28156058/aging-and-caloric-restriction-impact-adipose-tissue-adiponectin-and-circulating-lipids
#8
Karl N Miller, Maggie S Burhans, Josef P Clark, Porsha R Howell, Michael A Polewski, Tyler M DeMuth, Kevin W Eliceiri, Mary J Lindstrom, James M Ntambi, Rozalyn M Anderson
Adipose tissue expansion has been associated with system-wide metabolic dysfunction and increased vulnerability to diabetes, cancer, and cardiovascular disease. A reduction in adiposity is a hallmark of caloric restriction (CR), an intervention that extends longevity and delays the onset of these same age-related conditions. Despite these parallels, the role of adipose tissue in coordinating the metabolism of aging is poorly defined. Here, we show that adipose tissue metabolism and secretory profiles change with age and are responsive to CR...
February 3, 2017: Aging Cell
https://www.readbyqxmd.com/read/28147277/regulation-of-serine-threonine-kinase-akt-activation-by-nad-dependent-deacetylase-sirt7
#9
Jia Yu, Bo Qin, Fengying Wu, Sisi Qin, Somaira Nowsheen, Shan Shan, Jacqueline Zayas, Huadong Pei, Zhenkun Lou, Liewei Wang
The Akt pathway is a central regulator that promotes cell survival in response to extracellular signals. Depletion of SIRT7, an NAD(+)-dependent deacetylase that is the least-studied sirtuin, is known to significantly increase Akt activity in mice through unknown mechanisms. In this study, we demonstrate that SIRT7 depletion in breast cancer cells results in Akt hyper-phosphorylation and increases cell survival following genotoxic stress. Mechanistically, SIRT7 specifically interacts with and deacetylates FKBP51 at residue lysines 28 and 155 (K28 and K155), resulting in enhanced interactions among FKBP51, Akt, and PHLPP, as well as Akt dephosphorylation...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28143522/aspirin-intervention-for-the-reduction-of-colorectal-cancer-risk-aspired-a-study-protocol-for-a-randomized-controlled-trial
#10
David A Drew, Samantha M Chin, Katherine K Gilpin, Melanie Parziale, Emily Pond, Madeline M Schuck, Kathleen Stewart, Meaghan Flagg, Crystal A Rawlings, Vadim Backman, Peter J Carolan, Daniel C Chung, Francis P Colizzo, Matthew Freedman, Manish Gala, John J Garber, Curtis Huttenhower, Dmitriy Kedrin, Hamed Khalili, Douglas S Kwon, Sanford D Markowitz, Ginger L Milne, Norman S Nishioka, James M Richter, Hemant K Roy, Kyle Staller, Molin Wang, Andrew T Chan
BACKGROUND: Although aspirin is recommended for the prevention of colorectal cancer, the specific individuals for whom the benefits outweigh the risks are not clearly defined. Moreover, the precise mechanisms by which aspirin reduces the risk of cancer are unclear. We recently launched the ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED) trial to address these uncertainties. METHODS/DESIGN: ASPIRED is a prospective, double-blind, multidose, placebo-controlled, biomarker clinical trial of aspirin use in individuals previously diagnosed with colorectal adenoma...
February 1, 2017: Trials
https://www.readbyqxmd.com/read/28135088/role-of-reactive-oxygen-species-ros-in-therapeutics-and-drug-resistance-in-cancer-and-bacteria
#11
Dharmaraja T Allimuthu
Evading persistent drug resistance in cancer and bacteria to most of the commercially used drugs is necessary to restore the human health settings. A distinct property of cancer phenotype is enhanced glucose metabolism and oxidative stress from normal cells. Reactive oxygen species (ROS) are metabolic by-products of aerobic respiration and are responsible for maintaining redox homeostasis in cells. Maintaining the redox balance in cancerous cells are found to be critical for their survival, which is modulated by reduced thiols and reducing cofactors NAD(P)H...
January 30, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28122359/tumor-associated-nadh-oxidase-tnox-nad-sirtuin-1-axis-contributes-to-oxaliplatin-induced-apoptosis-of-gastric-cancer-cells
#12
Huei-Yu Chen, Hsiao-Ling Cheng, Yi-Hui Lee, Tien-Ming Yuan, Shi-Wen Chen, You-Yu Lin, Pin Ju Chueh
Oxaliplatin belongs to the platinum-based drug family and has shown promise in cancer treatment. The major mechanism of action of platinum compounds is to form platinum-DNA adducts, leading to DNA damage and apoptosis. Accumulating evidence suggests that they might also target non-DNA molecules for their apoptotic activity. We explored the effects of oxaliplatin on a tumor-associated NADH oxidase (tNOX) in gastric cancer lines. In AGS cells, we found that the oxaliplatin-inhibited tNOX effectively attenuated the NAD+/NADH ratio and reduced the deacetylase activity of an NAD+-dependent sirtuin 1, thereby enhancing p53 acetylation and apoptosis...
January 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099487/metabolic-imaging-of-head-and-neck-cancer-organoids
#13
Amy T Shah, Tiffany M Heaster, Melissa C Skala
Head and neck cancer patients suffer from toxicities, morbidities, and mortalities, and these ailments could be minimized through improved therapies. Drug discovery is a long, expensive, and complex process, so optimized assays can improve the success rate of drug candidates. This study applies optical imaging of cell metabolism to three-dimensional in vitro cultures of head and neck cancer grown from primary tumor tissue (organoids). This technique is advantageous because it measures cell metabolism using intrinsic fluorescence from NAD(P)H and FAD on a single cell level for a three-dimensional in vitro model...
2017: PloS One
https://www.readbyqxmd.com/read/28087461/low-glucose-stress-decreases-cellular-nadh-and-mitochondrial-atp-in-colonic-epithelial-cancer-cells-influence-of-mitochondrial-substrates
#14
Magdalena L Circu, Ronald E Maloney, Tak Yee Aw
In this study, we investigated how colonic epithelial cells maintained pyridine nucleotide (NADH/NAD(+)) redox homeostasis upon acute metabolic variation imposed by glucose deprivation or supplementation with mitochondrial substrates, succinate and malate/glutamate (M/G). Our results showed that low glucose caused cellular NADH/NAD(+) redox imbalance that diminished lactate dehydrogenase (LDH) activity and resulted in lower lactate contents. The concurrent activation of malic enzyme (ME) suggested a role for malate in preserving cellular pyruvate that remained unchanged at low glucose...
February 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28073696/spop-promotes-sirt2-degradation-and-suppresses-non-small-cell-lung-cancer-cell-growth
#15
Jie Luo, Yu-Chen Bao, Xian-Xiu Ji, Bin Chen, Qin-Fang Deng, Song-Wen Zhou
SIRT2 is a NAD-dependent deacetylase and inhibition of SIRT2 has a broad anticancer activity. Here we report that SPOP binds to SIRT2 and mediates its degradation by the 26S proteasome, which can be blocked by MG132 treatment. We also found that the levels of SPOP significantly decreased, while the levels of SIRT2 significantly increased in non-small cell lung cancer (NSCLC) cell lines, compared to normal bronchial epithelial cell line and NSCLC specimens, compared to the paired non-tumor lung tissue. Furthermore, SPOP can suppress NSCLC cell growth...
January 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28073422/-research-advances-in-the-association-between-deacetylase-sirtuin3-and-liver-diseases
#16
J Yu, C Chen, W X Wang
The deacetylase Sirtuin 3 (SIRT3) is a member of the Sirtuins mainly located in the mitochondrial matrix, and as a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, it can regulate cellular energy metabolism and oxidative stress-related pathways. The liver is the largest solid organ in the human body and plays a very important role in substance metabolism. Based on the features of SIRT3, it is closely associated with the development and progression of certain liver diseases. This article reviews the research advances in the role of SIRT3 in non-alcoholic fatty liver disease, liver cancer, and hepatic ischemia-reperfusion injury...
December 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28069826/endostatin-inhibits-androgen-independent-prostate-cancer-growth-by-suppressing-nuclear-receptor-mediated-oxidative-stress
#17
Joo Hyoung Lee, Minsung Kang, Hong Wang, Gurudatta Naik, James A Mobley, Guru Sonpavde, W Timothy Garvey, Victor M Darley-Usmar, Selvarangan Ponnazhagan
Androgen-deprivation therapy has been identified to induce oxidative stress in prostate cancer (PCa), leading to reactivation of androgen receptor (AR) signaling in a hormone-refractory manner. Thus, antioxidant therapies have gained attention as adjuvants for castration-resistant PCa. Here, we report for the first time that human endostatin (ES) prevents androgen-independent growth phenotype in PCa cells through its molecular targeting of AR and glucocorticoid receptor (GR) and downstream pro-oxidant signaling...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28063999/relationship-between-intracellular-ph-metabolic-co-factors-and-caspase-3-activation-in-cancer-cells-during-apoptosis
#18
Tatiana F Sergeeva, Marina V Shirmanova, Olga A Zlobovskaya, Alena I Gavrina, Varvara V Dudenkova, Maria M Lukina, Konstantin A Lukyanov, Elena V Zagaynova
A complex cascade of molecular events occurs in apoptotic cells but cell-to-cell variability significantly complicates determination of the order and interconnections between different processes. For better understanding of the mechanisms of programmed cell death, dynamic simultaneous registration of several parameters is required. In this paper we used multiparameter fluorescence microscopy to analyze energy metabolism, intracellular pH and caspase-3 activation in living cancer cells in vitro during staurosporine-induced apoptosis...
January 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28052592/innocent-but-deadly-nontoxic-organoiridium-catalysts-promote-selective-cancer-cell-death
#19
Lu Yang, Sohini Bose, Anh H Ngo, Loi H Do
We demonstrate that nontoxic organoiridum complexes can selectively chemosensitize cancer cells toward platinum antiproliferative agents. Treatment of human cancer cells (breast, colon, eye/retina, head/neck, lung, ovary, and blood) with the iridium chemosensitizers led to lowering of the 50 % growth inhibition concentration (IC50 ) of the Pt drug carboplatin by up to ∼30-50 %. Interestingly, non-cancer cells were mostly resistant to the chemosensitizing effects of the iridium complexes. Cell culture studies indicate that cancer cells that were administered with Ir show significantly higher reactive oxygen species concentrations as well as NAD(+) /NADH ratios (oxidized vs...
January 4, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28052347/apoptotic-effects-of-bovine-apo-lactoferrin-on-hela-tumor-cells
#20
Carla Luzi, Fabrizia Brisdelli, Roberto Iorio, Argante Bozzi, Veronica Carnicelli, Antonio Di Giulio, Anna Rita Lizzi
Lactoferrin (Lf), a cationic iron-binding glycoprotein of 80 kDa present in body secretions, is known as a compound with marked antimicrobial activity. In the present study, the apoptotic effect of iron-free bovine lactoferrin (apo-bLf) on human epithelial cancer (HeLa) cells was examined in association with reactive oxygen species and glutathione (GSH) levels. Apoptotic effect of iron-free bovine lactoferrin inhibited the growth of HeLa cells after 48 hours of treatment while the diferric-bLf was ineffective in the concentration range tested (from 1 to 12...
January 2017: Cell Biochemistry and Function
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