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https://www.readbyqxmd.com/read/29051480/nox4-functions-as-a-mitochondrial-energetic-sensor-coupling-cancer-metabolic-reprogramming-to-drug-resistance
#1
Karthigayan Shanmugasundaram, Bijaya K Nayak, William E Friedrichs, Dharam Kaushik, Ronald Rodriguez, Karen Block
The molecular mechanisms that couple glycolysis to cancer drug resistance remain unclear. Here we identify an ATP-binding motif within the NADPH oxidase isoform, NOX4, and show that ATP directly binds and negatively regulates NOX4 activity. We find that NOX4 localizes to the inner mitochondria membrane and that subcellular redistribution of ATP levels from the mitochondria act as an allosteric switch to activate NOX4. We provide evidence that NOX4-derived reactive oxygen species (ROS) inhibits P300/CBP-associated factor (PCAF)-dependent acetylation and lysosomal degradation of the pyruvate kinase-M2 isoform (PKM2)...
October 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29050764/pharmacokinetic-studies-of-a-three-component-complex-that-repurposes-the-front-line-antibiotic-isoniazid-against-mycobacterium-tuberculosis
#2
Thomas J Manning, Kyle Wilkerson, Taylor Holder, Andrew Carson Bartley, Chelsea Jackson, Sydney Plummer, Dennis Phillips, Logan Krajewski, Greg Wylie
The frontline tuberculosis (Tb) antibiotic isoniazid has been repurposed using a three component complex aimed at increasing the delivery efficiency and adding new avenues to its mechanism of action. This study focuses on pharmacokinetic studies of the isoniazid-sucrose-copper (II)-PEG-3350 complex. The assays include the Plasma Protein Binding Assay (85.8%), Caco-2 Permeability Assay (B→APapp, 0.13 × 10(-6) cm/s), Cytochrome P450 Inhibition Assay (i.e. CYP2B6, IC50 = 7.26 μM), In vitro microsomal Stability Assay (t1/2 NADPH-Dependent > 240 min), and HepG2 Cytotoxicity (no toxicity)...
December 2017: Tuberculosis
https://www.readbyqxmd.com/read/29048637/leptin-induces-ros-via-nox5-in-healthy-and-neoplastic-mammary-epithelial-cells
#3
Sinda Mahbouli, Audrey Der Vartanian, Sophie Ortega, Stéphanie Rougé, Marie-Paule Vasson, Adrien Rossary
NADPH oxidase (NOX) complexes (a family of seven isoforms) drive cellular ROS production in patho-logical processes such as cancer. NOX-driven ROS production is involved in cell mechanisms from signalling to oxidative stress. Leptin, an adipokine overexpressed in obese patients, has been investigated in studies on breast carcinogenesis, but its effects on oxidative stress remain largely unexplored, especially in breast cancer. The study used three human mammary epithelial cell models presenting different neoplastic status (healthy primary HMECs, neoplastic MCF-7 cells and neoplastic MDA-MB-231 cells) to determine the effects of leptin on short-term ROS production and to characterize the enzymes involved...
September 27, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29039574/tgf-%C3%AE-1-induced-cell-migration-in-pancreatic-carcinoma-cells-is-rac1-and-nox4-dependent-and-requires-rac1-and-nox4-dependent-activation-of-p38%C3%A2-mapk
#4
David Witte, Tobias Bartscht, Roland Kaufmann, Ralph Pries, Utz Settmacher, Hendrik Lehnert, Hendrik Ungefroren
Transforming growth factor (TGF)-β promotes epithelial-mesenchymal transition and cell invasion of cancer cells in part through the small GTPase RAC1. Since RAC1 can signal through reactive oxygen species (ROS), we probed the role of the ROS-producing NADPH oxidase (NOX) and p38 mitogen-activated protein kinase (MAPK) in mediating TGF-β1/RAC1-driven random cell migration (chemokinesis). Although the NOX isoforms NOX2, 4, 5, 6, and RAC1 were readily detectable by RT-PCR in pancreatic ductal adenocarcinoma (PDAC)-derived Panc1 and Colo357 cells, only NOX4 and RAC1 were expressed at higher levels comparable to those in peripheral blood monocytes...
October 12, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29038291/cystine-uptake-through-the-cystine-glutamate-antiporter-xct-triggers-glioblastoma-cell-death-under-glucose-deprivation
#5
Takeo Goji, Kazuhiko Takahara, Manabu Negishi, Hironori Katoh
Oncogenic signaling in cancer cells alters glucose uptake and utilization to supply sufficient energy and biosynthetic intermediates for survival and sustained proliferation. Oncogenic signaling also prevents oxidative stress and cell death caused by increased production of reactive oxygen species (ROS). However, elevated glucose metabolism in cancer cells, especially in glioblastoma, results in the cells becoming sensitive to glucose deprivation (i.e. in high glucose dependence), which rapidly induces cell death...
October 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29032312/advanced-oxidation-protein-products-induce-s-phase-arrest-of-hepatocytes-via-the-ros-dependent-%C3%AE-catenin-cdk2-mediated-pathway
#6
Shibo Sun, Fang Xie, Xiaoping Xu, Qing Cai, Qifan Zhang, Zhonglin Cui, Yujian Zheng, Jie Zhou
Liver regeneration has important clinical importance in the setting of partial hepatectomy (PH). Following PH, quiescent hepatocytes can reenter cell cycle to restore liver mass. Hepatocyte cell cycle progression, as the basic motivations of liver regeneration, can be disrupted by multiple pathological factors such as oxidative stress. This study aimed to evaluate the role of advanced oxidation protein products (AOPP) in S-phase arrest in hepatocytes. Serum AOPP level were measured during the perioperative period of PH in 33 patients with hepatocellular carcinoma (HCC)...
October 6, 2017: Redox Biology
https://www.readbyqxmd.com/read/29024812/inhibition-of-pyruvate-carboxylase-by-1%C3%AE-25-dihydroxyvitamin-d-promotes-oxidative-stress-in-early-breast-cancer-progression
#7
Tomasz Wilmanski, Xuanzhu Zhou, Wei Zheng, Aparna Shinde, Shawn S Donkin, Michael Wendt, John R Burgess, Dorothy Teegarden
Maintaining reductive-oxidative (redox) balance is an essential feature in breast cancer cell survival, with cellular metabolism playing an integral role in maintaining redox balance through its supply of reduced NADPH. In the present studies, the effect of 1,25-dihydroxyvitamin D (1,25(OH)2D) on redox balance was investigated in early stages of breast cancer. Treatment with 1,25(OH)2D promoted oxidative stress in MCF10A-ras and MCF10A-ErbB2 breast epithelial cells, as measured by the decreased ratios of NADPH/NADP+ and reduced to oxidized glutathione (GSH/GSSG)...
October 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28993239/regulation-of-nadph-oxidase-nox4-by-delta-iodolactone-il-%C3%AE-in-thyroid-cancer-cells
#8
Thomasz Lisa, Romina Oglio, Leonardo Salvarredi, Marina Perona, Luciano Rossich, Silvia Copelli, Mario Pisarev, Guillermo Juvenal
INTRODUCTION: Iodine is not used only by the thyroid to synthesize thyroid hormones but also directly influences a number of thyroid parameters such as thyroid proliferation and function. Several iodinated lipids, biosynthesized by the thyroid, were postulated as intermediaries in the action of iodide. Among these, iodolactone (IL-δ) and 2-iodohexadecanal (2-IHDA) have shown to inhibit several thyroid parameters. The antiproliferative effect of IL-δ is not restricted to the thyroid gland...
October 6, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28990413/nadph-oxidases-and-their-roles-in-skin-homeostasis-and-carcinogenesis
#9
Jana Rudolf, Houssam Raad, Alain Taieb, Hamid Reza Rezvani
SIGNIFICANCE: Skin protects the body from dehydration, pathogens and external mutagens. NADPH oxidases are central components for regulating the cellular redox balance. There is increasing evidence indicating that reactive oxygen species generated by members of this enzyme family play important roles in the physiology and pathophysiology of the skin. Recent Advances: NADPH oxidases are active producers of reactive oxygen species such as superoxide and hydrogen peroxide. Different isoforms are found in virtually all tissues...
October 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28985560/ferroptosis-a-regulated-cell-death-nexus-linking-metabolism-redox-biology-and-disease
#10
REVIEW
Brent R Stockwell, José Pedro Friedmann Angeli, Hülya Bayir, Ashley I Bush, Marcus Conrad, Scott J Dixon, Simone Fulda, Sergio Gascón, Stavroula K Hatzios, Valerian E Kagan, Kay Noel, Xuejun Jiang, Andreas Linkermann, Maureen E Murphy, Michael Overholtzer, Atsushi Oyagi, Gabriela C Pagnussat, Jason Park, Qitao Ran, Craig S Rosenfeld, Konstantin Salnikow, Daolin Tang, Frank M Torti, Suzy V Torti, Shinya Toyokuni, K A Woerpel, Donna D Zhang
Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10...
October 5, 2017: Cell
https://www.readbyqxmd.com/read/28965082/butaselen-prevents-hepatocarcinogenesis-and-progression-through-inhibiting-thioredoxin-reductase-activity
#11
Xiaoqing Zheng, Weiwei Ma, Ruoxuan Sun, Hanwei Yin, Fei Lin, Yuxi Liu, Wei Xu, Huihui Zeng
Hepatocellular carcinoma (HCC) accounts for most of primary liver cancer, of which five-year survival rate remains low and chemoprevention has become a strategy to reduce disease burden of HCC. We aim to explore the in vivo chemopreventive effect of an organoselenium-containing compound butaselen (BS) against hepatocarcinogenesis and its underlying mechanisms. Pre- and sustained BS treatment (9, 18 and 36mg/Kg BS) could dose-dependently inhibit chronic hepatic inflammation, fibrosis, cirrhosis and HCC on murine models with 24 weeks treatment scheme...
September 22, 2017: Redox Biology
https://www.readbyqxmd.com/read/28959211/oxidative-stress-in-oral-diseases-understanding-its-relation-with-other-systemic-diseases
#12
REVIEW
Jaya Kumar, Seong Lin Teoh, Srijit Das, Pasuk Mahakknaukrauh
Oxidative stress occurs in diabetes, various cancers, liver diseases, stroke, rheumatoid arthritis, chronic inflammation, and other degenerative diseases related to the nervous system. The free radicals have deleterious effect on various organs of the body. This is due to lipid peroxidation and irreversible protein modification that leads to cellular apoptosis or programmed cell death. During recent years, there is a rise in the oral diseases related to oxidative stress. Oxidative stress in oral disease is related to other systemic diseases in the body such as periodontitis, cardiovascular, pancreatic, gastric, and liver diseases...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28947826/neferine-ameliorates-cardiomyoblast-apoptosis-induced-by-doxorubicin-possible-role-in-modulating-nadph-oxidase-ros-mediated-nf%C3%AE%C2%BAb-redox-signaling-cascade
#13
Lohanathan Bharathi Priya, Rathinasamy Baskaran, Chih-Yang Huang, Viswanadha Vijaya Padma
Doxorubicin (DOX) mediated cardiomyopathy is a major challenge in cancer chemotherapy. Redox-cycling of doxorubicin by flavoenzymes makes the heart more vulnerable to oxidative stress leading to cardiac dysfunction. The present study evaluates the role of neferine, a bisbenzylisoquinoline alkaloid, in curbing the molecular consequences of DOX-exposure in H9c2 cardiomyoblasts. Neferine pre-treatment increased cell viability upon DOX-exposure. DOX activates NADPH oxidase subunits, (p22phox, p47phox, gp91phox) as the primary event followed by peak in [Ca(2+)]i accumulation by 2 h, ROS by 3 h and activated ERK1/2 and p38 MAPKinases, time dependently along with the activation and translocation of NFκB and up-regulated COX2 and TNF-α expressions...
September 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28937798/dual-effects-of-resveratrol-on-cell-death-and-proliferation-of-colon-cancer-cells
#14
Álvaro San Hipólito-Luengo, Antonio Alcaide, Mariella Ramos-González, Elena Cercas, Susana Vallejo, Alejandra Romero, Elena Talero, Carlos F Sánchez-Ferrer, Virginia Motilva, Concepción Peiró
Colorectal cancer remains a main cause of deaths worldwide, and novel agents are being searched to treat this disease. Polyphenols have emerged as promising therapeutic tools in cancer. Resveratrol (3,5,4'-trihydoxy-trans-stilbene) induces cell death in different tumor cell lines, and it also stimulates the proliferation of specific breast and prostate cancer cell lines. Here, we studied the impact of resveratrol over a 100-fold concentration range on cell death and proliferation of HT-29 colorectal adenocarcinoma cells...
September 22, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28914765/statin-and-bisphosphonate-induce-starvation-in-fast-growing-cancer-cell-lines
#15
Heidrun Karlic, Florian Haider, Roman Thaler, Silvia Spitzer, Klaus Klaushofer, Franz Varga
Statins and bisphosphonates are increasingly recognized as anti-cancer drugs, especially because of their cholesterol-lowering properties. However, these drugs act differently on various types of cancers. Thus, the aim of this study was to compare the effects of statins and bisphosphonates on the metabolism (NADP⁺/NADPH-relation) of highly proliferative tumor cell lines from different origins (PC-3 prostate carcinoma, MDA-MB-231 breast cancer, U-2 OS osteosarcoma) versus cells with a slower proliferation rate like MG-63 osteosarcoma cells...
September 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28894215/gene-expression-of-nox-family-members-and-their-clinical-significance-in-hepatocellular-carcinoma
#16
Hyuk Soo Eun, Sang Yeon Cho, Jong Seok Joo, Sun Hyung Kang, Hee Seok Moon, Eaum Seok Lee, Seok Hyun Kim, Byung Seok Lee
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex-derived reactive oxygen species (ROS) promote chronic liver inflammation and remodeling that can drive hepatocellular carcinoma development. The role of NOX expression in hepatocellular carcinoma (HCC) has been partially investigated; however, the clinical relevance of collective or individual NOX family member expression for HCC survival remains unclear. Here, we obtained NOX mRNA expression data for 377 HCC samples and 21 normal liver controls from the TCGA data portal and performed Kaplan-Meier survival, gene ontology functional enrichment, and gene set enrichment analyses...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28875417/chlorogenic-acid-regulates-apoptosis-and-stem-cell-marker-related-gene-expression-in-a549-human-lung-cancer-cells
#17
Kazuo Yamagata, Yuri Izawa, Daiki Onodera, Motoki Tagami
Previous studies indicated that chlorogenic acid, a compound present in many fruits and vegetables, has anti-cancer activities. We report that chlorogenic acid regulates the expression of apoptosis-related genes and self-renewal-related stem cell markers in cancer cells. The lung cancer cell line A549 was cultured with or without chlorogenic acid. The presence of chlorogenic acid decreased cell proliferation as measured by MTT activity. Polymerase chain reaction (PCR) showed that treatment of cells with chlorogenic acid reduced the expression of BCL2 but increased that of both BAX and CASP3...
September 5, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28866862/acetylshikonin-is-a-novel-non-selective-cytochrome-p450-inhibitor
#18
Jong Cheol Shon, Nguyen Minh Phuc, Won Cheol Kim, Jae Kyung Heo, Zhexue Wu, Hyunyoung Lee, Kwang-Hyeon Liu
Acetylshikonin is biologically active compound with anti-cancer and anti-inflammatory activity, which is isolated from the root of Lithospermum erythrorhizoma. We have recently discovered a inhibitory effect of acetylshikonin against CYP2J2 activity. Based on this result, we expanded our study to evaluate the inhibitory effects of acetylshikonin against nine different cytochrome P450 (P450) isoforms in human liver microsomes (HLMs) using substrate cocktails incubation assay. Acetylshikonin showed strong inhibitory effect against all P450s tested with IC50 values of 1...
September 3, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28852166/a-dynamic-metabolic-flux-analysis-of-myeloid-derived-suppressor-cells-confirms-immunosuppression-related-metabolic-plasticity
#19
Guillaume Goffaux, Iness Hammami, Mario Jolicoeur
Recent years have witnessed an increasing interest at understanding the role of myeloid-derived suppressor cells (MDSCs) in cancer-induced immunosuppression, with efforts to inhibit their maturation and/or their activity. We have thus modelled MDSCs central carbon metabolism and bioenergetics dynamic, calibrating the model using experimental data on in vitro matured mice bone marrow cells into MDSCs. The model was then used to probe the cells metabolic state and dynamics, performing a dynamic metabolic flux analysis (dMFA) study...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28851999/benzo-a-pyrene-induced-metabolic-shift-from-glycolysis-to-pentose-phosphate-pathway-in-the-human-bladder-cancer-cell-line-rt4
#20
Nisha Verma, Mario Pink, Stefan Boland, Albert W Rettenmeier, Simone Schmitz-Spanke
Benzo[a]pyrene (B[a]P), a well-known polyaromatic hydrocarbon, is known for its lung carcinogenicity, however, its role in bladder cancer development is still discussed. Comparative two-dimensional blue native SDS-PAGE analysis of protein complexes isolated from subcellular fractions of 0.5 µM B[a]P-exposed cells indicated a differential regulation of proteins involved in carbohydrate, fatty acid, and nucleotide metabolism, suggesting a possible metabolic flux redistribution. It appeared that B[a]P exposure led to a repression of enzymes (fructose-bisphosphate aldolase A, glucose-6-phosphate isomerase, lactate dehydrogenase) involved in glycolysis, and an up-regulation of proteins (glucose-6-phosphate 1-dehydrogenase, 6-phosphogluconolactonase) catalyzing the pentose phosphate pathway and one carbon metabolism (10-formyltetrahydrofolate dehydrogenase, bifunctional purine biosynthesis protein)...
August 29, 2017: Scientific Reports
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