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https://www.readbyqxmd.com/read/27902968/selenite-inhibits-glutamine-metabolism-and-induces-apoptosis-by-regulating-gls1-protein-degradation-via-apc-c-cdh1-pathway-in-colorectal-cancer-cells
#1
Junzhang Zhao, Rui Zhou, Kaiyuan Hui, Yang Yang, QiuYue Zhang, Yali Ci, Lei Shi, Caimin Xu, Fang Huang, Yu Hu
Glutaminolysis is important for metabolism and biosynthesis of cancer cells, and GLS is essential in the process. Selenite is widely regarded as a chemopreventive agent against cancer risk. Emerging evidence suggests that it also has chemotherapeutic potential in various cancer types, but the mechanism remains elusive. We demonstrate for the first time that supranutritional dose of selenite suppresses glutaminolysis by promoting GLS1 protein degradation and apoptosis. Mechanistically, selenite promotes association of APC/C-CDH1 with GLS1 and leads to GLS1 degradation by ubiquitination, this process is related to induction of PTEN expression...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27835669/the-glutaminase-1-inhibitor-968-enhances-dihydroartemisinin-mediated-antitumor-efficacy-in-hepatocellular-carcinoma-cells
#2
Diancheng Wang, Gang Meng, Meihong Zheng, Yonghui Zhang, Aiping Chen, Junhua Wu, Jiwu Wei
Reprogrammed metabolism and redox homeostasis are potential targets of cancer therapy. Our previous study demonstrated that the kidney form of glutaminase (GLS1) is highly expressed in hepatocellular carcinoma (HCC) cells and can be used as a target for effective anticancer therapy. Dihydroartemisinin (DHA) increases intracellular reactive oxygen species (ROS) levels leading to cytotoxicity in cancer cells. However, the heterogeneity of cancer cells often leads to differing responses to oxidative lesions. For instance, cancer cells with high ratio of GSH/GSSG, a critical ROS scavenger, are resistant to ROS-induced cytotoxicity...
2016: PloS One
https://www.readbyqxmd.com/read/27830010/glutaminase-inhibitor-compound-968-inhibits-cell-proliferation-and-sensitizes-paclitaxel-in-ovarian-cancer
#3
Lingqin Yuan, Xiugui Sheng, Leslie H Clark, Lu Zhang, Hui Guo, Hannah M Jones, Adam K Willson, Paola A Gehrig, Chunxiao Zhou, Victoria L Bae-Jump
Our overall goal was to investigate the anti-tumor activity of the glutaminase 1 (GLS1) Inhibitor compound 968 in ovarian cancer cells. The human ovarian cancer cell lines, HEY, SKOV3 and IGROV-1 were used. Cell proliferation was assessed by MTT assay after treatment with compound 968. Cell cycle progression and Annexin V expression were evaluated using Cellometer. Western blotting was performed to determine changes in GLS1, cellular stress and cell cycle checkpoints. Reactive oxygen species (ROS) and glutamate dehydrogenase (GDH) activity were assessed by ELISA assay...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27806325/inhibiting-glutaminase-in-acute-myeloid-leukemia-metabolic-dependency-of-selected-aml-subtypes
#4
Polina Matre, Juliana Velez, Rodrigo Jacamo, Yuan Qi, Xiaoping Su, Tianyu Cai, Steven M Chan, Alessia Lodi, Shannon R Sweeney, Helen Ma, Richard Eric Davis, Natalia Baran, Torsten Haferlach, Xiaohua Su, Elsa Renee Flores, Doriann Gonzalez, Sergej Konoplev, Ismael Samudio, Courtney DiNardo, Ravi Majeti, Aaron D Schimmer, Weiqun Li, Taotao Wang, Stefano Tiziani, Marina Konopleva
Metabolic reprogramming has been described as a hallmark of transformed cancer cells. In this study, we examined the role of the glutamine (Gln) utilization pathway in acute myeloid leukemia (AML) cell lines and primary AML samples. Our results indicate that a subset of AML cell lines is sensitive to Gln deprivation. Glutaminase (GLS) is a mitochondrial enzyme that catalyzes the conversion of Gln to glutamate. One of the two GLS isoenzymes, GLS1 is highly expressed in cancer and encodes two different isoforms: kidney (KGA) and glutaminase C (GAC)...
October 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27793929/inhibition-of-glutaminolysis-inhibits-cell-growth-via-down-regulating-mtorc1-signaling-in-lung-squamous-cell-carcinoma
#5
Xulu Ye, Qiliang Zhou, Yoshifumi Matsumoto, Masato Moriyama, Shun Kageyama, Masaaki Komatsu, Seijiro Satoh, Masanori Tsuchida, Yasuo Saijo
BACKGROUND/AIM: Inhibition of glutaminolysis has been reported as a promising therapeutic strategy to target several solid carcinomas. We aimed to investigate the effects of glutaminolysis on cell proliferation in lung squamous cell carcinoma cell lines and to explore the potential of targeting glutaminolysis as an anticancer strategy. MATERIALS AND METHODS: Glutamine (Gln) dependence was assessed in six lung squamous cell carcinoma cell lines. Cell proliferation, mammalian target of rapamycin complex 1 (mTORC1) activity and the induction of autophagy were assessed after inhibition of glutaminolysis via Gln depletion or glutaminase (GLS) inhibition...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27548520/vascular-stiffness-mechanoactivates-yap-taz-dependent-glutaminolysis-to-drive-pulmonary-hypertension
#6
Thomas Bertero, William M Oldham, Katherine A Cottrill, Sabrina Pisano, Rebecca R Vanderpool, Qiujun Yu, Jingsi Zhao, Yiyin Tai, Ying Tang, Ying-Yi Zhang, Sofiya Rehman, Masataka Sugahara, Zhi Qi, John Gorcsan, Sara O Vargas, Rajan Saggar, Rajeev Saggar, W Dean Wallace, David J Ross, Kathleen J Haley, Aaron B Waxman, Victoria N Parikh, Teresa De Marco, Priscilla Y Hsue, Alison Morris, Marc A Simon, Karen A Norris, Cedric Gaggioli, Joseph Loscalzo, Joshua Fessel, Stephen Y Chan
Dysregulation of vascular stiffness and cellular metabolism occurs early in pulmonary hypertension (PH). However, the mechanisms by which biophysical properties of the vascular extracellular matrix (ECM) relate to metabolic processes important in PH remain undefined. In this work, we examined cultured pulmonary vascular cells and various types of PH-diseased lung tissue and determined that ECM stiffening resulted in mechanoactivation of the transcriptional coactivators YAP and TAZ (WWTR1). YAP/TAZ activation modulated metabolic enzymes, including glutaminase (GLS1), to coordinate glutaminolysis and glycolysis...
September 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27467144/t-helper-cell-activation-and-expansion-is-sensitive-to-glutaminase-inhibition-under-both-hypoxic-and-normoxic-conditions
#7
Zeynep Sener, Fritjof H Cederkvist, Roman Volchenkov, Halvor L Holen, Bjørn S Skålhegg
Immune responses often take place where nutrients and O2 availability are limited. This has an impact on T cell metabolism and influences activation and effector functions. T cell proliferation and expansion are associated with increased consumption of glutamine which is needed in a number of metabolic pathways and regulate various physiological processes. The first step in endogenous glutamine metabolism is reversible and is regulated by glutaminase (GLS1 and GLS2) and glutamine synthase (GLUL). There are two isoforms of GLS1, Kidney type glutaminase (KGA) and Glutaminase C (GAC)...
2016: PloS One
https://www.readbyqxmd.com/read/27462778/pdha1-gene-knockout-in-prostate-cancer-cells-results-in-metabolic-reprogramming-towards-greater-glutamine-dependence
#8
Yaqing Li, Xiaoran Li, Xiaoli Li, Yali Zhong, Yasai Ji, Dandan Yu, Mingzhi Zhang, Jian-Guo Wen, Hongquan Zhang, Mariusz Adam Goscinski, Jahn M Nesland, Zhenhe Suo
Alternative pathways of metabolism endowed cancer cells with metabolic stress. Inhibiting the related compensatory pathways might achieve synergistic anticancer results. This study demonstrated that pyruvate dehydrogenase E1α gene knockout (PDHA1 KO) resulted in alterations in tumor cell metabolism by rendering the cells with increased expression of glutaminase1 (GLS1) and glutamate dehydrogenase1 (GLUD1), leading to an increase in glutamine-dependent cell survival. Deprivation of glutamine induced cell growth inhibition, increased reactive oxygen species and decreased ATP production...
July 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27447554/expression-of-glutamine-metabolism-related-proteins-in-thyroid-cancer
#9
Hye Min Kim, Yu Kyung Lee, Ja Seung Koo
PURPOSE: This study aimed to investigate the expression of glutamine metabolism-related protein in tumor and stromal compartments among the histologic subtypes of thyroid cancer. RESULTS: GLS1 and GDH expression in tumor and stromal compartments were the highest in AC than in other subtypes. Tumoral ASCT2 expression was higher in MC but lower in FC (p < 0.001). In PTC, tumoral GLS1 and tumoral GDH expression was higher in the conventional type than in the follicular variant (p = 0...
July 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27411920/inhibition-of-the-oxidative-stress-induced-mir-23a-protects-the-human-retinal-pigment-epithelium-rpe-cells-from-apoptosis-through-the-upregulation-of-glutaminase-and-glutamine-uptake
#10
Dan-Dan Li, Bin-Wu Zhong, Hai-Xia Zhang, Hong-Yan Zhou, Jie Luo, Yang Liu, Gui-Chun Xu, Chun-Sheng Luan, Jun Fang
The degeneration of retinal pigment epithelium (RPE) cells in the sub retinal pigment epithelial space and choroid is an initial pathological characteristic for the age-related macular degeneration which is the leading cause of severe vision loss in old people. Moreover, oxidative stress is implicated as a major inducer of RPE cell death. Here, we assessed the correlation between the H2O2-induced RPE cell death and glutamine metabolism. We found under low glutamine supply (20 %), the ARPE-19 cells were more susceptive to H2O2-induced apoptosis...
October 2016: Molecular Biology Reports
https://www.readbyqxmd.com/read/27338638/glutaminase-1-inhibition-reduces-thymidine-synthesis-in-nsclc
#11
Jae-Seon Lee, Joon H Kang, Seon-Hyeong Lee, Chang-Hun Lee, Jaekyoung Son, Soo-Youl Kim
We found that non-small cell lung cancer (NSCLC) is remarkably sensitive to the regulation of glutamine supply by testing the metabolic dependency of 11 cancer cell lines against regulation of glycolysis, autophagy, fatty acid synthesis, and glutamine supply. Glutamine is known as a key supplement of cancer cell growth that is converted to α-ketoglutarate for anabolic biogenesis via glutamate by glutaminase 1 (GLS1). GLS1 inhibition using 10 μM of bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) showed about 50% cell growth arrest by SRB assay...
August 26, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27268090/dependence-on-glutamine-uptake-and-glutamine-addiction-characterize-myeloma-cells-a-new-attractive-target
#12
Marina Bolzoni, Martina Chiu, Fabrizio Accardi, Rosanna Vescovini, Irma Airoldi, Paola Storti, Katia Todoerti, Luca Agnelli, Gabriele Missale, Roberta Andreoli, Massimiliano G Bianchi, Manfredi Allegri, Amelia Barilli, Francesco Nicolini, Albertina Cavalli, Federica Costa, Valentina Marchica, Denise Toscani, Cristina Mancini, Eugenia Martella, Valeria Dall'Asta, Gaetano Donofrio, Franco Aversa, Ovidio Bussolati, Nicola Giuliani
The importance of glutamine (Gln) metabolism in multiple myeloma (MM) cells and its potential role as a therapeutic target are still unknown, although it has been reported that human myeloma cell lines (HMCLs) are highly sensitive to Gln depletion. In this study, we found that both HMCLs and primary bone marrow (BM) CD138(+) cells produced large amounts of ammonium in the presence of Gln. MM patients have lower BM plasma Gln with higher ammonium and glutamate than patients with indolent monoclonal gammopathies...
August 4, 2016: Blood
https://www.readbyqxmd.com/read/27010459/structural-analysis-of-free-n-glycans-in-%C3%AE-glucosidase-mutants-of-saccharomyces-cerevisiae-lack-of-the-evidence-for-the-occurrence-of-catabolic-%C3%AE-glucosidase-acting-on-the-n-glycans
#13
Tanim Jabid Hossain, Yoichiro Harada, Hiroto Hirayama, Haruna Tomotake, Akira Seko, Tadashi Suzuki
Saccharomyces cerevisiae produces two different α-glucosidases, Glucosidase 1 (Gls1) and Glucosidase 2 (Gls2), which are responsible for the removal of the glucose molecules from N-glycans (Glc3Man9GlcNAc2) of glycoproteins in the endoplasmic reticulum. Whether any additional α-glucosidases playing a role in catabolizing the glucosylated N-glycans are produced by this yeast, however, remains unknown. We report herein on a search for additional α-glucosidases in S. cerevisiae. To this end, the precise structures of cytosolic free N-glycans (FNGs), mainly derived from the peptide:N-glycanase (Png1) mediated deglycosylation of N-glycoproteins were analyzed in the endoplasmic reticulum α-glucosidase-deficient mutants...
2016: PloS One
https://www.readbyqxmd.com/read/26985303/glutaminase-gls1-inhibitors-as-potential-cancer-treatment
#14
Ahmed F Abdel-Magid
No abstract text is available yet for this article.
March 10, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/26894601/blockage-of-glutaminolysis-enhances-the-sensitivity-of-ovarian-cancer-cells-to-pi3k-mtor-inhibition-involvement-of-stat3-signaling
#15
Lili Guo, Bo Zhou, Zhengqing Liu, Ying Xu, Hao Lu, Meng Xia, Ensong Guo, Wanying Shan, Gang Chen, Changyu Wang
The PI3K/Akt/mTOR axis in ovarian cancer is frequently activated and implicated in tumorigenesis. Specific targeting of this pathway is therefore an attractive therapeutic approach for ovarian cancer. However, ovarian cancer cells are resistant to PP242, a dual inhibitor of mTORC1 and mTORC2. Interestingly, blockage of GLS1 with a selective inhibitor, CB839, or siRNA dramatically sensitized the PP242-induced cell death, as evident from increased PARP cleavage. The anti-cancer activity of CB-839 and PP242 was abrogated by the addition of the TCA cycle product α-ketoglutarate, indicating the critical function of GLS1 in ovarian cancer cell survival...
August 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/26807954/correction-fmirna-192-and-mirna-204-directly-suppress-lncrna-hottip-and-interrupt-gls1-mediated-glutaminolysis-in-hepatocellular-carcinoma
#16
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pgen.1005726.].
January 2016: PLoS Genetics
https://www.readbyqxmd.com/read/26778975/genetic-pharmacotherapy-as-an-early-cns-drug-development-strategy-testing-glutaminase-inhibition-for-schizophrenia-treatment-in-adult-mice
#17
Susana Mingote, Justine Masson, Celia Gellman, Gretchen M Thomsen, Chyuan-Sheng Lin, Robert J Merker, Inna Gaisler-Salomon, Yvonne Wang, Rachel Ernst, René Hen, Stephen Rayport
Genetic pharmacotherapy is an early drug development strategy for the identification of novel CNS targets in mouse models prior to the development of specific ligands. Here for the first time, we have implemented this strategy to address the potential therapeutic value of a glutamate-based pharmacotherapy for schizophrenia involving inhibition of the glutamate recycling enzyme phosphate-activated glutaminase. Mice constitutively heterozygous for GLS1, the gene encoding glutaminase, manifest a schizophrenia resilience phenotype, a key dimension of which is an attenuated locomotor response to propsychotic amphetamine challenge...
2015: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/26771232/dlx-2-and-glutaminase-upregulate-epithelial-mesenchymal-transition-and-glycolytic-switch
#18
Su Yeon Lee, Hyun Min Jeon, Min Kyung Ju, Eui Kyong Jeong, Cho Hee Kim, Hye Gyeong Park, Song Iy Han, Ho Sung Kang
Most cancer cells depend on enhanced glucose and glutamine (Gln) metabolism for growth and survival. Oncogenic metabolism provides biosynthetic precursors for nucleotides, lipids, and amino acids; however, its specific roles in tumor progression are largely unknown. We previously showed that distal-less homeobox-2 (Dlx-2), a homeodomain transcription factor involved in embryonic and tumor development, induces glycolytic switch and epithelial-mesenchymal transition (EMT) by inducing Snail expression. Here we show that Dlx-2 also induces the expression of the crucial Gln metabolism enzyme glutaminase (GLS1), which converts Gln to glutamate...
February 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/26751560/glutaminase-2-is-a-novel-negative-regulator-of-small-gtpase-rac1-and-mediates-p53-function-in-suppressing-metastasis
#19
Cen Zhang, Juan Liu, Yuhan Zhao, Xuetian Yue, Yu Zhu, Xiaolong Wang, Hao Wu, Felix Blanco, Shaohua Li, Gyan Bhanot, Bruce G Haffty, Wenwei Hu, Zhaohui Feng
Glutaminase (GLS) isoenzymes GLS1 and GLS2 are key enzymes for glutamine metabolism. Interestingly, GLS1 and GLS2 display contrasting functions in tumorigenesis with elusive mechanism; GLS1 promotes tumorigenesis, whereas GLS2 exhibits a tumor-suppressive function. In this study, we found that GLS2 but not GLS1 binds to small GTPase Rac1 and inhibits its interaction with Rac1 activators guanine-nucleotide exchange factors, which in turn inhibits Rac1 to suppress cancer metastasis. This function of GLS2 is independent of GLS2 glutaminase activity...
January 11, 2016: ELife
https://www.readbyqxmd.com/read/26710269/mirna-192-corrected-and-mirna-204-directly-suppress-lncrna-hottip-and-interrupt-gls1-mediated-glutaminolysis-in-hepatocellular-carcinoma
#20
Yunxia Ge, Xiaodan Yan, Yiguang Jin, Xinyu Yang, Xiang Yu, Liqing Zhou, Sichong Han, Qipeng Yuan, Ming Yang
Accumulated evidence demonstrated that long non-coding RNAs (lncRNAs) play a pivotal role in tumorigenesis. However, it is still largely unknown how these lncRNAs were regulated by small ncRNAs, such as microRNAs (miRNAs), at the post-transcriptional level. We here use lncRNA HOTTIP as an example to study how miRNAs impact lncRNAs expression and its biological significance in hepatocellular carcinoma (HCC). LncRNA HOTTIP is a vital oncogene in HCC, one of the deadliest cancers worldwide. In the current study, we identified miR-192 and miR-204 as two microRNAs (miRNAs) suppressing HOTTIP expression via the Argonaute 2 (AGO2)-mediated RNA interference (RNAi) pathway in HCC...
December 2015: PLoS Genetics
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