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https://www.readbyqxmd.com/read/27922187/tomentosin-induces-telomere-shortening-and-caspase-dependant-apoptosis-in-cervical-cancer-cells
#1
Nawel Merghoub, Hassan El Btaouri, Laila Benbacer, Saïd Gmouh, Chantal Trentesaux, Bertrand Brassart, Mohammed Attaleb, Claudie Madoulet, Thomas Wenner, Saaid Amzazi, Hamid Morjani, Mohamed El Mzibri
Tomentosin, a natural sesquiterpene lactone purified from of Inula viscosa L., was investigated for its anti-proliferative, telomere shortening and apoptotic effects on human cervical cancer HeLa and SiHa cell lines. Tomentosin was found to inhibit the growth of SiHa and HeLa cell lines in dose and time-dependent manner (IC50 values of 7.10 ± 0.78µM and 5.87 ± 0.36µM, respectively after 96h of treatment). As evidenced by TTAGGG telomere length assay, tomentosin target specifically the telomeric overhang lengthening...
December 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27920426/crystal-structure-based-discovery-of-a-novel-synthesized-parp1-inhibitor-ol-1-with-apoptosis-inducing-mechanisms-in-triple-negative-breast-cancer
#2
Leilei Fu, Shuya Wang, Xuan Wang, Peiqi Wang, Yaxin Zheng, Dahong Yao, Mingrui Guo, Lan Zhang, Liang Ouyang
Poly (ADP-ribose) polymerase-1 (PARP1) is a highly conserved enzyme focused on the self-repair of cellular DNA damage. Until now, numbers of PARP inhibitors have been reported and used for breast cancer therapy in recent years, especially in TNBC. However, developing a new type PARP inhibitor with distinctive skeleton is alternatively promising strategy for TNBC therapy. In this study, based on co-crystallization studies and pharmacophore-docking-based virtual screening, we discovered a series of dihydrodibenzo[b,e]-oxepin compounds as PARP1 inhibitors...
December 2016: Scientific Reports
https://www.readbyqxmd.com/read/27919953/bishydroquinone-renieramycin-m-induces-apoptosis-of-human-lung-cancer-cells-through-a-mitochondria-dependent-pathway
#3
Tatchakorn Pinkhien, Arnatchai Maiuthed, Supakarn Chamni, Khanit Suwanborirux, Naoki Saito, Pithi Chanvorachote
BACKGROUND: Renieranycin M (RM), a bistetrahydro-isoquinolinequinone isolated from the Thai blue sponge, Xestospongia sp. was reported to be a potent anti-lung cancer agent. Modification at quinone ring enhanced apoptosis over necrosis. Thus, bishydroquinone renieramycin M (HQ-RM) was prepared and evaluated for apoptosis induction in lung cancer cells. METHODS: HQ-RM was examined for cytotoxicity and apoptosis induction in human lung cancer H292 cells by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazoliumbromide and Hoechst/propidium iodide staining, respectively...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919945/the-leloir-pathway-of-galactose-metabolism-a-novel-therapeutic-target-for-hepatocellular-carcinoma
#4
Manshu Tang, Enoabasi Etokidem, Kent Lai
Hepatocellular carcinoma (HCC) is one of the most lethal types of cancer worldwide, with poor prognosis and limited treatments. In order to identify novel therapeutic targets that will lead to development of effective therapies with manageable side effects, we tested the hypothesis that knocking-down galactokinase (GALK1) or galactose-1 phosphate uridylyltransferase (GALT) gene expression would control the growth of cultured hepatoma cells. Our results showed small interfering RNA (siRNA) against GALK1 or GALT inhibited the growth of HepG2 cells in culture...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27918638/small-molecule-microarray-based-discovery-of-parp14-inhibitors
#5
Bo Peng, Ann-Gerd Thorsell, Tobias Karlberg, Herwig Schüler, Shao Q Yao
Poly(ADP-ribose) polymerases (PARPs) are key enzymes in a variety of cellular processes. Most small-molecule PARP inhibitors developed to date have been against PARP1, and suffer from poor selectivity. PARP14 has recently emerged as a potential therapeutic target, but its inhibitor development has trailed behind. Herein, we describe a small molecule microarray-based strategy for high-throughput synthesis, screening of >1000 potential bidentate inhibitors of PARPs, and the successful discovery of a potent PARP14 inhibitor H10 with >20-fold selectivity over PARP1...
December 5, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27917671/-the-role-of-oxidative-stress-in-the-development-of-diabetic-neuropathy
#6
Ferenc Sztanek, Ágnes Molnárné Molnár, Zoltán Balogh
Diabetic neuropathy may be one of the most common and severe complications of diabetes mellitus. Oxidative stress plays a pivotal role in the development of microvascular complications of diabetes. The majority of related pathways like polyol and hexosamine, advanced glycation end products, poly-ADP-ribose polymerase, and protein kinase-C all originated from initial oxidative stress. In this review, the authors present the current oxidative stress hypothesis in diabetes mellitus and summarize the pathophysiological mechanisms of diabetic neuropathy associated with increased oxidative stress...
December 2016: Orvosi Hetilap
https://www.readbyqxmd.com/read/27917619/practical-guidance-on-the-use-of-olaparib-capsules-as-maintenance-therapy-for-women-with-brca-mutations-and-platinum-sensitive-recurrent-ovarian-cancer
#7
REVIEW
Michael Friedlander, Susana Banerjee, Linda Mileshkin, Clare Scott, Catherine Shannon, Jeffrey Goh
Olaparib is the first oral poly(ADP-ribose) polymerase inhibitor to be approved as maintenance monotherapy for treatment of patients with platinum-sensitive relapsed BRCA-mutated (BRCAm) serous ovarian cancer. This review provides practical guidance on the use of olaparib (capsule formulation) in the maintenance setting. The article focuses on the key toxicities that can arise with olaparib therapy and recommendations for their management. Nausea, vomiting, fatigue and anemia are the most commonly reported adverse events in olaparib clinical trials and are generally mild to moderate and transient in nature in most patients...
December 2016: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27916418/knockdown-of-tktl1-additively-complements-cisplatin-induced-cytotoxicity-in-nasopharyngeal-carcinoma-cells-by-regulating-the-levels-of-nadph-and-ribose-5-phosphate
#8
Yuke Dong, Ming Wang
BACKGROUND: Transketolase-like 1 (TKTL1) plays an important role in pentose phosphate pathway (PPP) branch, the main pathway generating nicotinamide adenine dinucleotide phosphate (NADPH) and nucleotides for DNA synthesis. TKTL1 is closely related to DNA damage and has a close relationship with incidence and progression of cancers. Cisplatin is the main chemotherapeutic drug by inducing DNA damage. Whether TKTL1 knockdown additively complements cisplatin-induced cytotoxicity in nasopharyngeal carcinoma cells, however, remains largely undefined...
December 1, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27915984/structure-function-and-evolution-of-clostridium-botulinum-c2-and-c3-toxins-insight-to-poultry-and-veterinary-vaccines
#9
P Chellapandi, A Prisilla
Clostridium botulinum group III strains are able to produce cytotoxins, C2 toxin and C3 exotoxin, along with botulinum neurotoxin types C and D. C2 toxin and C3 exotoxin produced from this organism are the most important members of bacterial ADP-ribosyltransferase superfamily. Both toxins have distinct pathophysiological functions in the avian and mammalian hosts. The members of this superfamily transfer an ADP-ribose moiety of NAD+ to specific eukaryotic target proteins. The present review describes the structure, function and evolution aspects of these toxins with a special emphasis to the development of veterinary vaccines...
December 1, 2016: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/27915154/lipopolysaccharides-stimulated-macrophage-products-enhance-withaferin-a-induced-apoptosis-via-activation-of-caspases-and-inhibition-of-nf-%C3%AE%C2%BAb-pathway-in-human-cancer-cells
#10
Liang Piao, Zhao Canguo, Lu Wenjie, Cheng Xiaoli, Shi Wenli, Lu Li
Macrophages, as a major cellular component in tumor microenvironment, play an important role in tumor progression. However, their roles in modulation of cytotoxic chemotherapy are still not fully understood. Here, we investigated the influence of Lipoplysaccharides (LPS)-stimulated macrophage products (LSMP) on Withaferin A (WA), a natural compound that derived from the medicinal plant Withania somnifera, as an antitumor agent in human breast cancer cells MDA-MB-231 and prostate cancer cells PC-3. Our results revealed that LSMP may enhance WA-induced apoptosis in both cell lines, the underlying mechanisms of which are closely associated with activation of caspase-8, -9 and -3, cleavage of poly ADP-ribose polymerase (PARP), as well as specifically inhibiting the translocation of nuclear factor-κB (NF-κB) and down-regulation of anti-apoptotic proteins X-linked inhibitor of apoptosis protein (XIAP) and inhibitor of apoptosis protein (cIAP1/2)...
December 1, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27913206/mag-fluo4-in-t-cells-imaging-of-intra-organelle-free-ca-2-concentrations
#11
Björn-Philipp Diercks, Ralf Fliegert, Andreas H Guse
Ca(2+) signaling is a major signal transduction pathway involved in T cell activation, but also in apoptosis of T cells. Since T cells make use of several Ca(2+)-mobilizing second messengers, such as nicotinic acid adenine dinucleotide phosphate, d-myo-inositol 1,4,5-trisphosphate, and cyclic ADP-ribose, we intended to analyze luminal Ca(2+) concentration upon cell activation. Mag-Fluo4/AM, a low-affinity Ca(2+) dye known to localize to the endoplasmic reticular lumen in many cell types, showed superior brightness and bleaching stability, but, surprisingly, co-localized with mito-tracker, but not with ER-tracker in Jurkat T cells...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27912065/phosphoribosylation-of-ubiquitin-promotes-serine-ubiquitination-and-impairs-conventional-ubiquitination
#12
Sagar Bhogaraju, Sissy Kalayil, Yaobin Liu, Florian Bonn, Thomas Colby, Ivan Matic, Ivan Dikic
Conventional ubiquitination involves the ATP-dependent formation of amide bonds between the ubiquitin C terminus and primary amines in substrate proteins. Recently, SdeA, an effector protein of pathogenic Legionella pneumophila, was shown to mediate NAD-dependent and ATP-independent ubiquitin transfer to host proteins. Here, we identify a phosphodiesterase domain in SdeA that efficiently catalyzes phosphoribosylation of ubiquitin on a specific arginine via an ADP-ribose-ubiquitin intermediate. SdeA also catalyzes a chemically and structurally distinct type of substrate ubiquitination by conjugating phosphoribosylated ubiquitin to serine residues of protein substrates via a phosphodiester bond...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27911769/reductive-carboxylation-is-a-major-metabolic-pathway-in-the-retinal-pigment-epithelium
#13
Jianhai Du, Aya Yanagida, Kaitlen Knight, Abbi L Engel, Anh Huan Vo, Connor Jankowski, Martin Sadilek, Van Thi Bao Tran, Megan A Manson, Aravind Ramakrishnan, James B Hurley, Jennifer R Chao
The retinal pigment epithelium (RPE) is a monolayer of pigmented cells that requires an active metabolism to maintain outer retinal homeostasis and compensate for oxidative stress. Using (13)C metabolic flux analysis in human RPE cells, we found that RPE has an exceptionally high capacity for reductive carboxylation, a metabolic pathway that has recently garnered significant interest because of its role in cancer cell survival. The capacity for reductive carboxylation in RPE exceeds that of all other cells tested, including retina, neural tissue, glial cells, and a cancer cell line...
December 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27910195/mulberrofuran-g-protects-ischemic-injury-induced-cell-death-via-inhibition-of-nox4-mediated-ros-generation-and-er-stress
#14
Sungeun Hong, Jaeyoung Kwon, Dong-Woo Kim, Hak Ju Lee, Dongho Lee, Woongchon Mar
The aim of this study was to investigate the neuroprotective effect of mulberrofuran G (MG) in in vitro and in vivo models of cerebral ischemia. MG was isolated from the root bark of Morus bombycis. MG inhibited nicotinamide adenine dinucleotide phosphate oxidase (NOX) enzyme activity and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced NOX4 protein expression in SH-SY5Y cells. MG inhibited the expression of activated caspase-3 and caspase-9 and cleaved poly adenine dinucleotide phosphate-ribose polymerase in OGD/R-induced SH-SY5Y cells...
December 2, 2016: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/27908594/rucaparib-in-relapsed-platinum-sensitive-high-grade-ovarian-carcinoma-ariel2-part-1-an-international-multicentre-open-label-phase-2-trial
#15
Elizabeth M Swisher, Kevin K Lin, Amit M Oza, Clare L Scott, Heidi Giordano, James Sun, Gottfried E Konecny, Robert L Coleman, Anna V Tinker, David M O'Malley, Rebecca S Kristeleit, Ling Ma, Katherine M Bell-McGuinn, James D Brenton, Janiel M Cragun, Ana Oaknin, Isabelle Ray-Coquard, Maria I Harrell, Elaina Mann, Scott H Kaufmann, Anne Floquet, Alexandra Leary, Thomas C Harding, Sandra Goble, Lara Maloney, Jeff Isaacson, Andrew R Allen, Lindsey Rolfe, Roman Yelensky, Mitch Raponi, Iain A McNeish
BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors have activity in ovarian carcinomas with homologous recombination deficiency. Along with BRCA1 and BRCA2 (BRCA) mutations genomic loss of heterozygosity (LOH) might also represent homologous recombination deficiency. In ARIEL2, we assessed the ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor. METHODS: ARIEL2 is an international, multicentre, two-part, phase 2, open-label study done at 49 hospitals and cancer centres in Australia, Canada, France, Spain, the UK, and the USA...
November 28, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27908544/inhibition-of-cartilage-degradation-and-suppression-of-pge2-and-mmps-expression-by-pomegranate-fruit-extract-in-a-model-of-posttraumatic-osteoarthritis
#16
Nahid Akhtar, Nazir M Khan, Omer S Ashruf, Tariq M Haqqi
OBJECTIVE: Osteoarthritis (OA) is characterized by cartilage degradation in the affected joints. Pomegranate fruit extract (PFE) inhibits cartilage degradation in vitro. The aim of this study was to determine whether oral consumption of PFE inhibits disease progression in rabbits with surgically induced OA. METHODS: OA was surgically induced in the tibiofemoral joints of adult New Zealand White rabbits. In one group, animals were fed PFE in water for 8 wk postsurgery...
January 2017: Nutrition
https://www.readbyqxmd.com/read/27907908/prevalence-and-clinical-significance-of-brca1-2-germline-and-somatic-mutations-in-taiwanese-patients-with-ovarian-cancer
#17
Angel Chao, Ting-Chang Chang, Nina Lapke, Shih-Ming Jung, Peter Chi, Chien-Hung Chen, Lan-Yan Yang, Cheng-Tao Lin, Huei-Jean Huang, Hung-Hsueh Chou, Jui-Der Liou, Shu-Jen Chen, Tzu-Hao Wang, Chyong-Huey Lai
Germline and somatic BRCA1/2 mutations define a subset of patients with ovarian cancer who may benefit from treatment with poly (ADP-ribose) polymerase inhibitors. Unfortunately, data on the frequency of BRCA1/2 germline mutations in Taiwanese patients with ovarian cancer are scarce, with the prevalence of somatic mutations being unknown. We aim to investigate the occurrence of BRCA1/2 mutations in 99 Taiwanese patients with ovarian cancer which included serous (n = 46), endometrioid (n = 24), and clear cell (n = 29) carcinomas...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27907199/identification-heterologous-expression-and-functional-characterization-of-bacillus-subtilis-yutf-a-had-superfamily-5-nucleotidase-with-broad-substrate-specificity
#18
Natalia P Zakataeva, Dmitriy V Romanenkov, Yuliya R Yusupova, Victoria S Skripnikova, Takayuki Asahara, Sergey V Gronskiy
5'-nucleotidases (EC 3.1.3.5) catalyze the hydrolytic dephosphorylation of 5'-ribonucleotides and 5'-deoxyribonucleotides as well as complex nucleotides, such as uridine 5'-diphosphoglucose (UDP-glucose), nicotinamide adenine dinucleotide and flavin adenine dinucleotide, to their corresponding nucleosides plus phosphate. These enzymes have been found in diverse species in intracellular and membrane-bound, surface-localized forms. Soluble forms of 5'-nucleotidases belong to the ubiquitous haloacid dehalogenase superfamily (HADSF) and have been shown to be involved in the regulation of nucleotide, nucleoside and nicotinamide adenine dinucleotide (NAD+) pools...
2016: PloS One
https://www.readbyqxmd.com/read/27905883/carbohydrate-metabolism-in-oenococcus-oeni-a-genomic-insight
#19
Alice Cibrario, Claire Peanne, Marine Lailheugue, Hugo Campbell-Sills, Marguerite Dols-Lafargue
BACKGROUND: Oenococcus oeni is the bacterial species that drives malolactic fermentation in most wines. Several studies have described a high intraspecific diversity regarding carbohydrate degradation abilities but the link between the phenotypes and the genes and metabolic pathways has been poorly described. RESULTS: A collection of 41 strains whose genomic sequences were available and representative of the species genomic diversity was analyzed for growth on 18 carbohydrates relevant in wine...
December 1, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27905606/a-qm-mm-study-of-the-reaction-mechanism-of-human-%C3%AE-ketoacyl-reductase
#20
Fabiola E Medina, Rui P P Neves, Maria J Ramos, Pedro A Fernandes
Human fatty acid synthase (hFAS) is a multifunctional enzyme involved in a wide diversity of biological functions. For instance, it is a precursor of phospholipids and other complex processes such as the de novo synthesis of long chain fatty acid. Human FAS is also a component of biological membranes and it is implicated in the overexpression of several types of cancers. In this work, we describe the catalytic mechanism of β-ketoreductase (KR), which is a catalytic domain of the hFAS enzyme that catalyzes the reduction of β-ketoacyl to β-hydroxyacyl with the concomitant oxidation of the NADPH cofactor...
December 1, 2016: Physical Chemistry Chemical Physics: PCCP
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