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3 bromopyruvate

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https://www.readbyqxmd.com/read/29581356/icos-signaling-controls-induction-and-maintenance-of-collagen-induced-arthritis
#1
Vincent Panneton, Sahar Bagherzadeh Yazdchi, Mariko Witalis, Jinsam Chang, Woong-Kyung Suh
ICOS is a key costimulatory receptor facilitating differentiation and function of follicular helper T cells and inflammatory T cells. Rheumatoid arthritis patients were shown to have elevated levels of ICOS+ T cells in the synovial fluid, suggesting a potential role of ICOS-mediated T cell costimulation in autoimmune joint inflammation. In this study, using ICOS knockout and knockin mouse models, we found that ICOS signaling is required for the induction and maintenance of collagen-induced arthritis (CIA), a murine model of rheumatoid arthritis...
March 26, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29561307/synergistic-in-vitro-effects-of-combining-an-antiglycolytic-3-bromopyruvate-and-a-bromodomain-4-inhibitor-on-u937-myeloid-leukemia-cells
#2
Nicolette Kapp, Xiao X Stander, Barend A Stander
This project investigated the in-vitro effects of a glycolytic inhibitor, 3-bromopyruvate (3-BrP), in combination with and a new in silico-designed inhibitor of the bromodomain-4 (BRD-4) protein, ITH-47, on the U937 acute myeloid leukemia cell line. 3-BrP is an agent that targets the altered metabolism of cancer cells by interfering with glucose metabolism in the glycolytic pathway. ITH-47 is an acetyl-lysine inhibitor that displaces bromdomain 4 proteins from chromatin by competitively binding to the acetyl-lysine recognition pocket of this bromodomain and extraterminal (BET) BRD protein, thereby preventing transcription of cancer-associated genes and further cell growth...
March 20, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29463225/glycolysis-is-essential-for-chemoresistance-induced-by-transient-receptor-potential-channel-c5-in-colorectal-cancer
#3
Teng Wang, Kuan Ning, Xu Sun, Chun Zhang, Lin-Fang Jin, Dong Hua
BACKGROUND: Elevated intracellular Ca2+ ([Ca2+ ]i ) level could lead to [Ca2+ ]i overload and promote apoptosis via different pathways. In our previously study, up-regulated expression of transient receptor potential canonical channel (TRPC5) was proven to increase [Ca2+ ]i level, and resulted in chemoresistance whereas not apoptosis in human colorectal cancer (CRC) cells. The ATP-dependent homeostatic maintenance of resting [Ca2+ ]i should be important in this process. Increased glycolysis was found to be an important adenosine triphosphate (ATP) source in cancer...
February 20, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29438555/autophagy-related-gene-atg13-is-involved-in-control-of-xylose-alcoholic-fermentation-in-the-thermotolerant-methylotrophic-yeast-ogataea-polymorpha
#4
Kostyantyn V Dmytruk, Justyna Ruchala, Dorota Grabek-Lejko, Czeslaw Puchalski, Nina V Bulbotka, Andriy A Sibirny
Lignocellulosic biomass belongs to main sustainable renewable sources for global energy supply. One of the main challenges in the conversion of saccharified lignocellulosic biomass into bioethanol is the utilization of xylose, since lignocellulosic feedstocks contain a significant amount of this pentose. The nonconventional thermotolerant yeast Ogataea polymorpha naturally ferments xylose to ethanol at elevated temperatures (45°C). Studying the molecular mechanisms of regulation of xylose metabolism is a promising way toward increased xylose conversion to ethanol...
February 9, 2018: FEMS Yeast Research
https://www.readbyqxmd.com/read/29386184/lysophosphatidic-acid-induces-metabolic-reprogramming-in-ovarian-cancer-via-a-pseudohypoxic-response
#5
Ji Hee Ha, Rangasudhagar Radhakrishnan, Muralidharan Jayaraman, Mingda Yan, Jeremy D Ward, Kar-Ming Fung, Katherine M Moxley, Anil K Sood, Ciro Isidoro, Priyabrata Mukherjee, Yong Sang Song, Danny N Dhanasekaran
Although hypoxia has been shown to reprogram cancer cells toward glycolytic shift, the identity of extrinsic stimuli that induce metabolic reprogramming independent of hypoxia, especially in ovarian cancer, is largely unknown. In this study, we use patient-derived ovarian cancer cells and high-grade serous ovarian cancer cell lines to demonstrate that lysophosphatidic acid (LPA), a lipid growth factor and GPCR ligand whose levels are substantially increased in ovarian cancer patients, triggers glycolytic shift in ovarian cancer cells...
January 31, 2018: Cancer Research
https://www.readbyqxmd.com/read/29299135/acquired-resistance-to-pi3k-mtor-inhibition-is-associated-with-mitochondrial-dna-mutation-and-glycolysis
#6
King Xin Koh, Gim Hwa Tan, Sarah Hong Hui Low, Mohd Feroz Mohd Omar, Min Ji Han, Barry Iacopetta, Ross Soo, Mounia Beloueche-Babari, Bhaskar Bhattacharya, Richie Soong
Acquired resistance (AQR) to drug treatment occurs frequently in cancer patients and remains an impediment to successful therapy. The aim of this study was to gain insight into how AQR arises following the application of PI3K/mTOR inhibitors. H1975 lung cancer cells with EGFR T790M mutations that confer resistance to EGFR inhibitors underwent prolonged treatment with the PI3K/mTOR inhibitor, BEZ235. Monoclonal cells with stable and increased resistance to BEZ235 were obtained after 8 months treatment. These AQR clones showed class-specific resistance to PI3K/mTOR inhibitors, reduced G1 cell cycle arrest and impedance of migration following PI3K/mTOR inhibition, reduced PTEN expression and increased Akt and S6RP phosphorylation...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29286239/suppression-of-tumor-energy-supply-by-liposomal-nanoparticle-mediated-inhibition-of-aerobic-glycolysis
#7
Yinlong Zhang, Jingyan Wei, Jiaqi Xu, Wei Sun Leong, Guangna Liu, Tianjiao Ji, Zhiqiang Cheng, Jing Wang, Jiayan Lang, Ying Zhao, Linhao You, Xiao Zhao, Taotao Wei, Greg J Anderson, Sheng Qi, Jing Kong, Guangjun Nie, Suping Li
Aerobic glycolysis enables cancer cells to rapidly take up nutrients (e.g., nucleotides, amino acids, and lipids) and incorporate them into the biomass needed to produce a new cell. In contrast to existing chemotherapy/radiotherapy strategies, inhibiting aerobic glycolysis to limit the adenosine 5'-triphosphate (ATP) yield is a highly efficient approach for suppressing tumor cell proliferation. However, most, if not all, current inhibitors of aerobic glycolysis cause significant adverse effects because of their nonspecific delivery and distribution to nondiseased organs, low bioavailability, and a narrow therapeutic window...
January 24, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29225201/3-bromopyruvate-as-a-potential-pharmaceutical-in-the-light-of-experimental-data
#8
Izabela Szczuka, Andrzej Gamian, Grzegorz Terlecki
3-Bromopyruvate (3-BrPA) is an halogenated analogue of pyruvic acid known for over four decades as an alkylating agent reacting with thiol groups of many proteins. It enters animal cells like a lactate: via monocarboxylic acid transporters. Increasing interest in this compound, in recent times, is mainly due to hopes associated with its anticancer action. It is based on the impairment of energy metabolism of tumor cells by inhibiting enzymes in the glycolysis pathway (hexokinase II, glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate kinase) and the oxidative phosphorylation (succinate dehydrogenase)...
December 8, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/29221953/antitumor-action-of-3-bromopyruvate-implicates-reorganized-tumor-growth-regulatory-components-of-tumor-milieu-cell-cycle-arrest-and-induction-of-mitochondria-dependent-tumor-cell-death
#9
Saveg Yadav, Praveen Kumar Kujur, Shrish Kumar Pandey, Yugal Goel, Babu Nandan Maurya, Ashish Verma, Ajay Kumar, Rana Pratap Singh, Sukh Mahendra Singh
Evidences demonstrate that metabolic inhibitor 3-bromopyruvate (3-BP) exerts a potent antitumor action against a wide range of malignancies. However, the effect of 3-BP on progression of the tumors of thymic origin remains unexplored. Although, constituents of tumor microenvironment (TME) plays a pivotal role in regulation of tumor progression, it remains unclear if 3-BP can alter the composition of the crucial tumor growth regulatory components of the external surrounding of tumor cells. Thus, the present investigation attempts to understand the effect of 3-BP administration to a host bearing a progressively growing tumor of thymic origin on tumor growth regulatory soluble, cellular and biophysical components of tumor milieu vis-à-vis understanding its association with tumor progression, accompanying cell cycle events and mode of cell death...
January 15, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29129690/monoterpenoid-perillyl-alcohol-impairs-metabolic-flexibility-of-candida-albicans-by-inhibiting-glyoxylate-cycle
#10
Moiz A Ansari, Zeeshan Fatima, Kamal Ahmad, Saif Hameed
The metabolic pathway such as glyoxylate cycle (GC) enables Candida albicans, to survive under glucose deficient conditions prevalent in the hostile niche. Thus its key enzymes (Isocitrate lyase; ICL and malate synthase; MLS) represent attractive targets against C. albicans. We have previously reported the antifungal potential of a natural monoterpenoid perillyl alcohol (PA). The present study uncovers additional role of PA as a potent GC inhibitor. We explored that PA phenocopied ICL1 deletion mutant and were hypersensitive under low carbon utilizing conditions...
January 1, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29115645/combined-18f-fdg%C3%A2-pet-ct-imaging-and-a-gastric-orthotopic-xenograft-model-in-nude-mice-are-used-to-evaluate-the-efficacy-of-glycolysis-targeted-therapy
#11
Ting-An Wang, Shu-Lin Xian, Xing-Yu Guo, Xiao-Dong Zhang, Yun-Fei Lu
As discovered by Warburg 80 years ago most malignant cells rely more on glycolysis than normal cells. The high rate of glycolysis provides faster ATP production and greater lactic acid for tumor proliferation and invasion, thus indicating a potential target in anticancer therapy. Our previous studies demonstrated that 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) inhibited tumor cell proliferation in vitro. However, the underlying mechanisms still warrant further investigation. In the present study, we employed the human SGC-7901 gastric cancer cell line, built an orthotopic xenograft model in nude mice, examined the treatment response by 18F-FDG PET/CT and investigated the mechanisms of 3-BrPA and SCT in vivo...
October 31, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29092648/tempo-phosphate-as-an-esr-tool-to-study-phosphate-transport
#12
Izabela Sadowska-Bartosz, Ireneusz Stefaniuk, Bogumił Cieniek, Grzegorz Bartosz
TEMPO-phosphate has been introduced as a phosphate analogue to study phosphate transport in erythrocytes. The nitroxide is reduced intracellularly upon entering the cells, the membrane transport being the rate-limiting step of the loss of ESR signal. The use of TEMPO-phosphate is convenient and avoids the hazard of radioactivity. We studied the inhibition of TEMPO-phosphate transport to human erythrocytes by various compounds. DIDS and SITS, inhibitors of Band 3, inhibited the TEMPO-phosphate transport. 1-cyano-4-hydroxycinnamic acid, inhibitor of monocarboxylate transporters, did not affect the permeation of TEMPO-phosphate...
November 27, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28994148/lincrna-p21-suppresses-development-of-human-prostate-cancer-through-inhibition-of-pkm2
#13
Xiaohai Wang, Yongzhi Xu, Xingjie Wang, Chenyi Jiang, Sha Han, Kai Dong, Mengjun Shen, Dongliang Xu
OBJECTIVES: Previously, we found that long intergenic non-coding RNA-p21 (lincRNA-p21) inhibited the development of human prostate cancer. However, the underlying molecular mechanisms are poorly understood. Here, we attempted to investigate the downstream targets of lincRNA-p21 in prostate cancer. MATERIALS AND METHODS: Expression of lincRNA-p21 and PKM2 was determined by qRT-PCR and Western blot. Lentivirus expressing shPKM2 or shCtrl was used to explore the role of PKM2 on the enhanced cell proliferation and glycolysis of lincRNA-p21-silenced prostate cancer cells...
December 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28969010/dual-inhibition-of-glycolysis-and-glutaminolysis-as-a-therapeutic-strategy-in-the-treatment-of-ovarian-cancer
#14
Li Sun, Yajie Yin, Leslie H Clark, Wenchuan Sun, Stephanie A Sullivan, Arthur-Quan Tran, Jianjun Han, Lu Zhang, Hui Guo, Esther Madugu, Tommy Pan, Amanda L Jackson, Joshua Kilgore, Hannah M Jones, Timothy P Gilliam, Chunxiao Zhou, Victoria L Bae-Jump
Cancer cell metabolism is required to support the biosynthetic demands of cell growth and cell division, and to maintain reduction oxidaton (redox) homeostasis. This study was designed to test the effects of glucose and glutamine on ovarian cancer cell growth and explore the inter-relationship between glycolysis and glutaminolysis. The SKOV3, IGROV-1 and Hey ovarian cancer cell lines were assayed for glucose, pyruvate and glutamine dependence by analyzing cytotoxicity, cell cycle progression, apoptosis and ATP production...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28939007/menadione-mediated-wst1-reduction-assay-for-the-determination-of-metabolic-activity-of-cultured-neural-cells
#15
Karsten Stapelfeldt, Eric Ehrke, Johann Steinmeier, Wiebke Rastedt, Ralf Dringen
Cellular reduction of tetrazolium salts to their respective formazans is frequently used to determine the metabolic activity of cultured cells as an indicator of cell viability. For membrane-impermeable tetrazolium salts such as WST1 the application of a membrane-permeable electron cycler is usually required to mediate the transfer of intracellular electrons for extracellular WST1 reduction. Here we demonstrate that in addition to the commonly used electron cycler M-PMS, menadione can also serve as an efficient electron cycler for extracellular WST1 reduction in cultured neural cells...
December 1, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28920175/chemoenzymatic-synthesis-of-3-phosphoadenosine-5-phosphosulfate-coupling-with-an-atp-regeneration-system
#16
Cuiying An, Long Zhao, Zhaojun Wei, Xianxuan Zhou
3'-Phosphoadenosine-5'-phosphosulfate (PAPS) is the obligate cosubstrate and source of the sulfonate group in the chemoenzymatic synthesis of heparin, a commonly used anticoagulant drug. Previously, using ATP as the substrate, we had developed a one-pot synthesis to prepare PAPS with 47% ATP conversion efficiency. During the reaction, 47% of ATP was converted into the by-product, ADP. Here, to increase the conversion ratio of ATP to PAPS, an ATP regeneration system was developed to couple with PAPS synthesis...
October 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28874966/characterization-of-acetate-transport-in-colorectal-cancer-cells-and-potential-therapeutic-implications
#17
Suellen Ferro, João Azevedo-Silva, Margarida Casal, Manuela Côrte-Real, Fatima Baltazar, Ana Preto
Acetate, together with other short chain fatty acids has been implicated in colorectal cancer (CRC) prevention/therapy. Acetate was shown to induce apoptosis in CRC cells. The precise mechanism underlying acetate transport across CRC cells membrane, that may be implicated in its selectivity towards CRC cells, is not fully understood and was addressed here. We also assessed the effect of acetate in CRC glycolytic metabolism and explored its use in combination with the glycolytic inhibitor 3-bromopyruvate (3BP)...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/28816773/synergistic-antitumor-effect-of-3-bromopyruvate-and-5-fluorouracil-against-human-colorectal-cancer-through-cell-cycle-arrest-and-induction-of-apoptosis
#18
Dianlong Chong, Linyan Ma, Fang Liu, Zhirui Zhang, Surong Zhao, Qiang Huo, Pei Zhang, Hailun Zheng, Hao Liu
3-Bromopyruvic acid (3-BP) is a well-known inhibitor of energy metabolism. It has been proposed as an anticancer agent as well as a chemosensitizer for use in combination with anticancer drugs. 5-Fluorouracil (5-FU) is the first-line chemotherapeutic agent for colorectal cancer; however, most patients develop resistance to 5-FU through various mechanisms. The aim of this study was to investigate whether 3-BP has a synergistic antitumor effect with 5-FU on human colorectal cancer cells. In our study, combined 3-BP and 5-FU treatment upregulated p53 and p21, whereas cyclin-dependent kinase CDK4 and CDK2 were downregulated, which led to G0/G1 phase arrest...
September 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28733531/dual-inhibition-of-glycolysis-and-glutaminolysis-as-a-therapeutic-strategy-in-the-treatment-of-ovarian-cancer
#19
Li Sun, Yajie Yin, Leslie H Clark, Wenchuan Sun, Stephanie A Sullivan, Arthur-Quan Tran, Jianjun Han, Lu Zhang, Hui Guo, Esther Madugu, Tommy Pan, Amanda L Jackson, Joshua Kilgore, Hannah M Jones, Timothy P Gilliam, Chunxiao Zhou, Victoria L Bae-Jump
Cancer cell metabolism is required to support the biosynthetic demands of cell growth and cell division, and to maintain reduction oxidaton (redox) homeostasis. This study was designed to test the effects of glucose and glutamine on ovarian cancer cell growth and explore the inter-relationship between glycolysis and glutaminolysis. The SKOV3, IGROV-1 and Hey ovarian cancer cell lines were assayed for glucose, pyruvate and glutamine dependence by analyzing cytotoxicity, cell cycle progression, apoptosis and ATP production...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28720669/muc1-mediated-metabolic-alterations-regulate-response-to-radiotherapy-in-pancreatic-cancer
#20
Venugopal Gunda, Joshua Souchek, Jaime Abrego, Surendra K Shukla, Gennifer D Goode, Enza Vernucci, Aneesha Dasgupta, Nina V Chaika, Ryan J King, Sicong Li, Shuo Wang, Fang Yu, Tadayoshi Bessho, Chi Lin, Pankaj K Singh
Purpose:MUC1, an oncogene overexpressed in multiple solid tumors, including pancreatic cancer, reduces overall survival and imparts resistance to radiation and chemotherapies. We previously identified that MUC1 facilitates growth-promoting metabolic alterations in pancreatic cancer cells. The present study investigates the role of MUC1-mediated metabolism in radiation resistance of pancreatic cancer by utilizing cell lines and in vivo models.Experimental Design: We used MUC1-knockdown and -overexpressed cell line models for evaluating the role of MUC1-mediated metabolism in radiation resistance through in vitro cytotoxicity, clonogenicity, DNA damage response, and metabolomic evaluations...
October 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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