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NAD+ AND cancer

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https://www.readbyqxmd.com/read/28780936/nad-deficits-in-age-related-diseases-and-cancer
#1
REVIEW
Amanda Garrido, Nabil Djouder
The phenomenon of aging has gained widespread attention in recent times. Although significant advances have been made to better understand aging and its related pathologies including cancer, there is not yet a clear mechanism explaining why diseases and cancer are inherent parts of the aging process. Finding a unifying equation that could bridge aging and its related diseases would allow therapeutic development and solve an immense human health problem to live longer and better. In this review, we discuss NAD(+) reduction as the central mechanism that may connect aging to its related pathologies and cancer...
August 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28780322/reduction-of-oxidative-damages-induced-by-titanium-dioxide-nanoparticles-correlates-with-induction-of-the-nrf2-pathway-by-gspe-supplementation-in-mice
#2
Linpeng Niu, Mengjiao Shao, Yuan Liu, Jinfeng Hu, Ruofan Li, Heran Xie, Lixiao Zhou, Lei Shi, Rong Zhang, Yujie Niu
Titanium dioxide nanoparticles (TiO2 NPs) are widely used to additives in cosmetics, pharmaceuticals, paints and foods. Recent studies have demonstrated that TiO2 NPs increased the risk of cancer and the mechanism might relate with oxidative stress. Grape seed procyanidin extract (GSPE) is a natural compound which has been demonstrated to possess a wide array of pharmacological and biochemical actions, including anti-inflammatory, anti-carcinogenic, and antioxidant properties. Our data show that GSPE prevents the changes of histopathology and biomarkers in heart, liver and kidney that occur in mice exposed to TiO2 NPs...
August 2, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28770670/potential-repositioning-of-exemestane-as-a-neuroprotective-agent-for-parkinson-s-disease
#3
Hyo Jin Son, Se Hee Han, Ji Ae Lee, Eun Jung Shin, Onyou Hwang
Parkinson's disease (PD) is a neurodegenerative disorder characterised by selective degeneration of the nigral dopaminergic neurons, and neuroinflammation and oxidative stress are believed to be involved in its pathogenesis. In the present study, we provide data that the synthetic steroid exemestane, which is currently being used to treat breast cancer, may be useful for PD therapy. In BV-2 microglial cells, exemestane activated the transcription factor Nrf2 and induced expression of the Nrf2-dependent genes that encode the antioxidant enzymes NAD(P)H: quinone oxidoreductase 1, haem oxygenase-1, and glutamylcysteine ligase...
June 2017: Free Radical Research
https://www.readbyqxmd.com/read/28766915/metabolomics-analysis-reveals-distinct-profiles-of-nonmuscle-invasive-and-muscle-invasive-bladder-cancer
#4
Divya Sahu, Yair Lotan, Bryan Wittmann, Bruce Neri, Donna E Hansel
Urothelial carcinoma is the most common form of bladder cancer, but pathway changes that occur with stage-wise progression have not been well defined. We used a metabolomics approach to identify potential metabolic pathways uniquely altered in normal urothelium, nonmuscle-invasive bladder cancer (NMIBC), and muscle-invasive bladder cancer (MIBC). We performed global metabolomic profiling using GC-mass spectrometry (MS) and LC-MS platforms to identify metabolite signatures between normal urothelium and high-grade urothelial carcinoma of different stages...
August 1, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28756225/identification-of-novel-resistance-mechanisms-to-nampt-inhibition-via-the-de-novo-nad-biosynthesis-pathway-and-nampt-mutation
#5
Jun Guo, Lloyd T Lam, Kenton L Longenecker, Mai H Bui, Kenneth B Idler, Keith B Glaser, Julie L Wilsbacher, Chris Tse, William N Pappano, Tzu-Hsuan Huang
Cancer cells have an unusually high requirement for the central and intermediary metabolite nicotinamide adenine dinucleotide (NAD(+)), and NAD(+) depletion ultimately results in cell death. The rate limiting step within the NAD(+) salvage pathway required for converting nicotinamide to NAD(+) is catalyzed by nicotinamide phosphoribosyltransferase (NAMPT). Targeting NAMPT has been investigated as an anti-cancer strategy, and several highly selective small molecule inhibitors have been found to potently inhibit NAMPT in cancer cells, resulting in NAD(+) depletion and cytotoxicity...
July 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28748640/expression-of-nad-p-h-quinone-dehydrogenase-1-nqo1-is-increased-in-the-endometrium-of-women-with-endometrial-cancer-and-women-with-polycystic-ovary-syndrome
#6
William Atiomo, Mohamad Nasir Shafiee, Caroline Chapman, Veronika M Metzler, Jad Abouzeid, Ayşe Latif, Amy Chadwick, Sarah Kitson, Vanitha N Sivalingam, Ian J Stratford, Catrin S Rutland, Jenny L Persson, Niels Ødum, Pablo Fuentes-Utrillia, Jennie N Jeyapalan, David M Heery, Emma J Crosbie, Nigel P Mongan
OBJECTIVE: Women with a prior history of polycystic ovary syndrome (PCOS) have an increased risk of endometrial cancer (EC). AIM: To investigate whether the endometrium of women with PCOS possess gene expression changes similar to those found in EC. DESIGN AND METHODS: Patients with EC, PCOS and control women unaffected by either PCOS or EC were recruited into a cross-sectional study at the Nottingham University Hospital, UK. For RNA sequencing, representative individual endometrial biopsies were obtained from women with EC, PCOS and a woman unaffected by PCOS or EC...
July 27, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28733523/preclinical-efficacy-of-the-novel-competitive-nampt-inhibitor-stf-118804-in-pancreatic-cancer
#7
Jair Machado Espindola-Netto, Claudia C S Chini, Mariana Tarragó, Enfeng Wang, Shamit Dutta, Krishnendu Pal, Debabrata Mukhopadhyay, Mauro Sola-Penna, Eduardo N Chini
NAD salvage is one of the pathways used to generate NAD in mammals. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in this pathway, uses nicotinamide (NAM) to generate nicotinamide mononucleotide (NMN). NMN is one of the main precursors of NAD synthesis in cells. Our previous study showed the importance of NAMPT in maintaining NAD levels in pancreatic ductal adenocarcinoma cells (PDAC), and that the NAMPT inhibitor FK866 decreased pancreatic cancer growth. We now tested the effect of STF-118804, a new highly specific NAMPT inhibitor, in models of pancreatic ductal adenocarcinoma...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28719017/contrasting-sirtuin-and-parp-activity-of-selected-2-4-6-trisubstituted-benzimidazoles
#8
Keng Yoon Yeong, Soo Choon Tan, Chun-Wai Mai, Chee-Onn Leong, Felicia Fei-Lei Chung, Yean Kee Lee, Chin Fei Chee, Noorsaadah Abdul Rahman
Both sirtuin and poly(ADP-ribose)polymerase (PARP) family of enzymes utilize NAD+ as co-substrate. Inhibitors of sirtuins and PARPs are important tools in drug discovery as they are reported to be linked to multiple diseases such as cancer. New potent sirtuin inhibitors (2,4,6-trisubstituted benzimidazole) were discovered from reported PARP inhibitor scaffold. Interestingly, the synthesized compounds have contrasting sirtuin and PARP-1 inhibitory activity. We showed that modification on benzimidazoles may alter their selectivity towards sirtuin or PARP-1 enzymes...
July 18, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28714938/taxifolin-activates-the-nrf2-anti-oxidative-stress-pathway-in-mouse-skin-epidermal-jb6-p-cells-through-epigenetic-modifications
#9
Haixue Kuang, Zhenqiu Tang, Chengyue Zhang, Zhibin Wang, Wenji Li, Chunjuan Yang, Qiuhong Wang, Bingyou Yang, Ah-Ng Kong
Nuclear factor erythroid-2 related factor 2 (Nrf2) is a vital transcription factor that regulates the anti-oxidative defense system. Previous reports suggested that the expression of the Nrf2 gene can be regulated by epigenetic modifications. The potential epigenetic effect of taxifolin (TAX), a potent cancer chemopreventive agent, in skin cancer chemoprotection is unknown. In this study, we investigated how Nrf2 is epigenetically regulated by TAX in JB6 P+ cells. TAX was found to inhibit the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced colony formation of JB6 P+ cells...
July 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28714034/inhibition-of-nampt-decreases-cell-growth-and-enhances-susceptibility-to-oxidative-stress
#10
Renhua Xu, Zhenwei Yuan, Lijuan Yang, Lele Li, Dan Li, Changjun Lv
Nicotinamide adenine dinucleotide (NAD) is an essential molecule for living organisms and plays a vital role in aging and age-associated diseases. In eukaryotic cells, cellular NAD is mainly generated by the scavenge pathway in which nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the formation of nicotinamide mononucleotide. Inhibition of NAMPT is a therapeutic strategy for cancer treatment. To explore the effects of NAMPT inhibition on cellular processes, cells were treated with 10 nM FK866, an NAMPT inhibitor, resulting in a decrease in the cellular NAD level, a lower growth rate, and enhanced susceptivity to oxidative stress as compared to the untreated cells...
July 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28713490/picroside-ii-shows-protective-functions-for-severe-acute-pancreatitis-in-rats-by-preventing-nf-%C3%AE%C2%BAb-dependent-autophagy
#11
Xuehua Piao, Baohai Liu, Lianyi Guo, Fanji Meng, Leming Gao
Picroside II, from the herb Picrorhiza scrophulariiflora Pennell, has antioxidant and anti-inflammatory activities. However, its function on severe acute pancreatitis (SAP) and molecular mechanism remains unknown. The effects of picroside II on the SAP induced by cerulean were investigated. SAP rats were treated with picroside II (25 mg/kg). The severity of SAP was evaluated by using biochemical and histological analyses. Pancreatic cancer cell PANC-1 was transfected with ptfLC3 (an indicator of autophagic activity), pcDNA3...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28707979/emerging-roles-for-sirt5-in-metabolism-and-cancer
#12
Lauren Rose Bringman-Rodenbarger, Angela H Guo, Costas A Lyssiotis, David B Lombard
SIGNIFICANCE: Developing evidence in the literature suggests that SIRT5 may be involved in metabolic reprogramming, an emerging hallmark of cancer by which neoplastic cells reconfigure their metabolism to support the anabolic demands of rapid cell division. Sirtuin 5 (SIRT5) is one of the seven members of the nicotinamide adenine dinucleotide (NAD+)-dependent sirtuin family of lysine deacylases. It removes succinyl, malonyl, and glutaryl groups from protein targets within the mitochondrial matrix and other subcellular compartments...
July 14, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28704830/sirtuins-in-skin-and-skin-cancers
#13
Liz Mariely Garcia-Peterson, Melissa Jean Wilking-Busch, Mary Ann Ndiaye, Christine Gaby Azer Philippe, Vijayasaradhi Setaluri, Nihal Ahmad
The sirtuins are a family of proteins that comprise class III of the histone deacetylases. These NAD+-dependent proteins have been found to be intricately involved in a variety of important and skin-relevant cellular functions and processes, including aging, UV damage response, oxidative stress, and wound repair. In addition, recent research is unraveling the role of sirtuins in a variety of skin diseases, including melanoma and nonmelanoma skin cancers. In this review, we provide a discussion on the potential roles and implications of different sirtuins in skin-specific cellular processes, which may have relevance to skin health and skin diseases...
2017: Skin Pharmacology and Physiology
https://www.readbyqxmd.com/read/28701960/role-of-mitochondrial-reverse-electron-transport-in-ros-signaling-potential-roles-in-health-and-disease
#14
REVIEW
Filippo Scialò, Daniel J Fernández-Ayala, Alberto Sanz
Reactive Oxygen Species (ROS) can cause oxidative damage and have been proposed to be the main cause of aging and age-related diseases including cancer, diabetes and Parkinson's disease. Accordingly, mitochondria from old individuals have higher levels of ROS. However, ROS also participate in cellular signaling, are instrumental for several physiological processes and boosting ROS levels in model organisms extends lifespan. The current consensus is that low levels of ROS are beneficial, facilitating adaptation to stress via signaling, whereas high levels of ROS are deleterious because they trigger oxidative stress...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28699906/genome-wide-functional-analysis-on-the-molecular-mechanism-of-specifically-biosynthesized-fluorescence-eu-complex
#15
Jing Ye, Xiawei Dong, Xuerui Jiang, Hui Jiang, Chen-Zhong Li, Xuemei Wang
Fluorescence imaging as an attractive diagnostic technique is widely employed for early diagnosis of cancer. Self-biosynthesized fluorescent Eu complex in situ in Hela cells have realized specifically and accurately fluorescence imaging for cancer cells. But the molecular mechanism of the in situ biosynthesized process is still unclear. In order to reveal this mechanism, we have investigated whole-genome expression profiles with cDNA microarray, incubated with Eu solution in Hela cells for 24 h. Methylthiazoltetrazolium (MTT) assay and laser confocal fluorescence microscopy study showed the low cytotoxicity and specifically fluorescence imaging of Eu complex in Hela cells...
July 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28698153/curcumin-prevents-cisplatin-induced-renal-alterations-in-mitochondrial-bioenergetics-and-dynamic
#16
Bibiana Ortega-Domínguez, Omar Emiliano Aparicio-Trejo, Fernando E García-Arroyo, Juan Carlos León-Contreras, Edilia Tapia, Eduardo Molina-Jijón, Rogelio Hernández-Pando, Laura Gabriela Sánchez-Lozada, Diana Barrera-Oviedo, José Pedraza-Chaverri
Cisplatin is widely used as chemotherapeutic agent for treatment of diverse types of cancer, however, acute kidney injury (AKI) is an important side effect of this treatment. Diverse mechanisms have been involved in cisplatin-induced AKI, such as oxidative stress, apoptosis and mitochondrial damage. On the other hand, curcumin is a polyphenol extracted from the rhizome of Curcuma longa L. Previous studies have shown that curcumin protects against the cisplatin-induced AKI; however, it is unknown whether curcumin can reduce alterations in mitochondrial bioenergetics and dynamic in this model...
September 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28695520/use-of-inosine-monophosphate-dehydrogenase-activity-assay-to-determine-the-specificity-of-parp-1-inhibitors
#17
Sajitha Anthony, Jeffrey R Peterson, Yingbiao Ji
Inosine monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme involved in purine nucleotide biosynthesis. It is responsible for catalyzing the oxidation of inosine monophosphate (IMP) into xanthosine monophosphate (XMP). Concurrently, the cofactor NAD(+) is reduced to NADH. Poly(ADP-ribose) polymerase 1 (PARP-1) also utilizes NAD(+) as a substrate to synthesize poly(ADP-ribose). It has been demonstrated that inhibition of PARP-1 activity can be an effective cancer therapeutic. However, most PARP-1 inhibitors, including olaparib, were developed as NAD(+) analogs...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28695517/high-throughput-colorimetric-assay-for-identifying-parp-1-inhibitors-using-a-large-small-molecule-collection
#18
Elena Kotova, Alexei V Tulin
Poly(ADP-ribose)polymerase 1 (PARP-1) protein became a popular target for treatment of several types of cancer. A number of PARP-1 inhibitors are currently in clinical trials. Most of them were designed competitors with NAD for a binding site on PARP-1 molecule. This strategy resulted in a discovery of mainly nucleotide-like PARP-1 inhibitors, which may target not only PARP-1 but also other pathways involving NAD and other nucleotides. Many cancer types demonstrate rapid development of resistance to NAD-like PARP-1 inhibitors...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28695506/using-clickable-nad-analogs-to-label-substrate-proteins-of-parps
#19
Lu Zhang, Hening Lin
ADP-ribosylation has been well known as an important posttranslational modification, which is catalyzed by a family of enzymes called poly(ADP-ribose) polymerases (PARPs). PARPs transfer of a single or multiple adenine diphosphate ribose (ADP-ribose) units from nicotinamide adenine dinucleotide (NAD(+)) to specific amino acids on substrate proteins. Through mono- or poly-ADP-ribosylation enzymatic activities, PARPs regulate various biological processes, including DNA damage repair, chromatin remodeling, transcriptional regulation, RNA processing and metabolism...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28695500/quantification-of-parp-activity-in-human-tissues-ex-vivo-assays-in-blood-cells-and-immunohistochemistry-in-human-biopsies
#20
Eszter M Horvath, Zsuzsanna K Zsengellér, Csaba Szabo
Poly(ADP-ribosyl)ation of proteins is a posttranslational modification mediated by poly(ADP-ribose) polymerases (PARPs) that use NAD(+) as substrate to form the negatively charged polymer of poly(ADP-ribose) (PAR). After DNA damage, PARP-1 is responsible for approximately 90% of the total cellular PARylation activity. Numerous studies showed activation of PARP-1 in various conditions associated with oxidative and nitrosative stress, such as ischemia-reperfusion injury, diabetes mellitus, and inflammation, and also proved the beneficial effects of PARP inhibitors...
2017: Methods in Molecular Biology
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