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Cancer AND glutamine

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https://www.readbyqxmd.com/read/28934309/increased-plasma-proline-concentrations-are-associated-with-sarcopenia-in-the-elderly
#1
Kenji Toyoshima, Marie Nakamura, Yusuke Adachi, Akira Imaizumi, Tomomi Hakamada, Yasuko Abe, Eiji Kaneko, Soiciro Takahashi, Kentaro Shimokado
BACKGROUND AND PURPOSE: Metabolome analyses have shown that plasma amino acid profiles reflect various pathological conditions, such as cancer and diabetes mellitus. It remains unclear, however, whether plasma amino acid profiles change in patients with sarcopenia. This study therefore aimed to investigate whether sarcopenia-specific changes occur in plasma amino acid profiles. METHODS: A total of 153 community-dwelling and seven institutionalized elderly individuals (56 men, 104 women; mean age, 77...
2017: PloS One
https://www.readbyqxmd.com/read/28928849/glutaminase-sustains-cell-survival-via-the-regulation-of-glycolysis-and-glutaminolysis-in-colorectal-cancer
#2
Zhou Song, Bo Wei, Canrong Lu, Peiyu Li, Lin Chen
Cancer cells remodel their metabolic programs towards aerobic glycolysis and elevated glutaminolysis to meet the requirement s of rapid proliferation. Understanding how cells sense and adapt to these changes may provide new targets for therapeutic intervention. Deamination of glutamine to glutamate by glutaminase (GLS1) is an essential step in glutaminolysis. The present study revealed that the loss of GLS1 expression by RNA interference or inhibitor decreased the proliferation and viability of colorectal cancer (CRC) cells...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927119/effect-of-glutamine-enriched-nutritional-support-on-intestinal-mucosal-barrier-function-mmp-2-mmp-9-and-immune-function-in-patients-with-advanced-gastric-cancer-during-perioperative-chemotherapy
#3
Juan Wang, Yanfen Li, Yuanling Qi
We studied the effects of glutamine-enriched nutritional support on intestinal mucosal barrier, matrix metalloproteinase (MMP)-2, MMP-9 and immune function during perioperative chemotherapy in patients with advanced gastric cancer. The study was conducted on 94 patients with advanced gastric cancer admitted from April 2015 to March 2016. They were randomly divided into observation and control groups, n=47. Control group was given basic nutritional support whereas glutamine-enriched nutritional support was given to patients in observation group...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28871132/an-lc-ms-approach-to-quantitative-measurement-of-ammonia-isotopologues
#4
Jessica B Spinelli, Liam P Kelley, Marcia C Haigis
Ammonia is a fundamental aspect of metabolism spanning all of phylogeny. Metabolomics, including metabolic tracing studies, are an integral part of elucidating the role of ammonia in these systems. However, current methods for measurement of ammonia are spectrophotometric, and cannot distinguish isotopologues of ammonia, significantly limiting metabolic tracing studies. Here, we describe a novel LC-MS-based method that quantitatively assesses both (14)N-and (15)N-isotopologues of ammonia in polar metabolite extracts...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28868350/the-answer-s-in-the-tail-myc-mrna-has-a-metabolic-sensor-that-supports-cancer-chemoresistance
#5
Nadine Royla, Stefan Kempa
Our recent study shows that the translation of MYC mRNA (mRNA) is controlled by its 3' untranslated region (UTR) in a process that depends on the availability of glutamine and levels of cellular nucleotides. Metabolic feedback protects cells from a lethal glutamine addiction and may compromise metabolic targeting of glutamine metabolism.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28858494/structure-activity-relationships-of-potent-targeted-covalent-inhibitors-that-abolish-both-the-transamidation-and-gtp-binding-activities-of-human-tissue-transglutaminase
#6
Abdullah Akbar, Nicole M R McNeil, Marie R Albert, Viviane Ta, Gautam Adhikary, Karine Bourgeois, Richard L Eckert, Jeffrey W Keillor
Human tissue transglutaminase (hTG2) is a multifunctional enzyme. It is primarily known for its calcium-dependent transamidation activity that leads to formation of an isopeptide bond between glutamine and lysine residues found on the surface of proteins, but it is also a GTP binding protein. Overexpression and unregulated hTG2 activity have been associated with numerous human diseases, including cancer stem cell survival and metastatic phenotype. Herein, we present a series of targeted covalent inhibitors (TCIs) based on our previously reported Cbz-Lys scaffold...
September 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28855722/real-time-monitoring-system-for-evaluating-the-acid-producing-activity-of-oral-squamous-cell-carcinoma-cells-at-different-environmental-ph
#7
Hiromitsu Morishima, Jumpei Washio, Jun Kitamura, Yuta Shinohara, Tetsu Takahashi, Nobuhiro Takahashi
This study aimed to establish a real-time monitoring system for evaluating the acid-producing activity of cells and the effects of microenvironmental pH on their metabolism. Oral squamous cell carcinoma (HSC-2, HSC-3) and normal (HaCaT) cells were used. Their acid-producing activity from glucose, glutamine, and glutamate was monitored at various pH values using a pH stat system. Their production of lactic acid and ammonia was also measured. The acid-producing activity was monitored successfully. Both the cancer and normal cells produced acids from glucose, glutamine, and glutamate...
August 30, 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
#8
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
https://www.readbyqxmd.com/read/28851309/differences-in-elongation-of-very-long-chain-fatty-acids-and-fatty-acid-metabolism-between-triple-negative-and-hormone-receptor-positive-breast-cancer
#9
Yuji Yamashita, Shin Nishiumi, Seishi Kono, Shintaro Takao, Takeshi Azuma, Masaru Yoshida
BACKGROUND: Triple-negative breast cancer (TN) is more aggressive than other subtypes of breast cancer and has a lower survival rate. Furthermore, detailed biological information about the disease is lacking. This study investigated characteristics of metabolic pathways in TN. METHODS: We performed the metabolome analysis of 74 breast cancer tissues and the corresponding normal breast tissues using LC/MS. Furthermore, we classified the breast cancer tissues into ER-positive, PgR-positive, HER2-negative breast cancer (EP+H-) and TN, and then the differences in their metabolic pathways were investigated...
August 29, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28847040/metabolic-effects-of-hedyotis-diffusa-on-rats-bearing-walker-256-tumor-revealed-by-nmr-based-metabolomics
#10
Zhiyong Wang, Kuo Gao, Can Xu, Jian Gao, Yujing Yan, Yingfeng Wang, Zhongfeng Li, Jianxin Chen
Hedyotis diffusa, a traditional Chinese herbal medicine, is widely used for oncotherapy and shows a positive effect in the clinical treatment. But its mechanism of anticancer activities is complicated and unclear. This study was undertaken to assess the therapeutic effects and reveal detailed mechanisms of H. diffusa for oncotherapy. A Walker 256 tumor-bearing rat model was established, and metabolomic profiles of plasma and urine were obtained from (1) H NMR technique. Multivariate statistical analysis methods were used to characterize the discriminating metabolites between control (C), Walker 256 tumor-bearing rats model (M), and H...
August 28, 2017: Magnetic Resonance in Chemistry: MRC
https://www.readbyqxmd.com/read/28846111/acetylation-is-essential-for-nuclear-heme-oxygenase-1-enhanced-tumor-growth-and-invasiveness
#11
F-F Hsu, M-T Chiang, F-A Li, C-T Yeh, W-H Lee, L-Y Chau
Overexpression of heme oxygenase-1 (HO-1), an endoplasmic reticulum-anchored enzyme, is observed in many cancers. HO-1 nuclear translocation has been shown to correlate with progression of several cancers. We recently reported that HO-1 is susceptible to intramembrane proteolysis and translocates to the nucleus to promote cancer growth and invasiveness without depending on its enzymatic activity. In the present study, we show that the HO-1 lacking C-terminal transmembrane segment (t-HO-1) was susceptible to acetylation by p300 and CREB-binding protein (CBP) histone acetyltransferase in the nucleus...
August 28, 2017: Oncogene
https://www.readbyqxmd.com/read/28839461/glutamic-pyruvate-transaminase-gpt2-promotes-tumorigenesis-of-breast-cancer-cells-by-activating-sonic-hedgehog-signaling
#12
Yuan Cao, Shu-Hai Lin, Yongbin Wang, Y Eugene Chin, Lan Kang, Jun Mi
Increased glutamine metabolism is a hallmark of cancer. Mitochondrial glutamic pyruvate transaminase (GPT2) catalyzes the reversible transamination between alanine and α-ketoglutarate (α-KG), also known as 2-oxoglutarate, to generate pyruvate and glutamate during cellular glutamine catabolism. However, the precise role of GPT2 in tumorigenesis remains elusive. Here, we report that in breast cancer tissue samples and breast cancer cell lines, GPT2 expression level was markedly elevated and correlated with the pathological grades of breast cancers...
2017: Theranostics
https://www.readbyqxmd.com/read/28835257/long-noncoding-rnas-coordinate-functions-between-mitochondria-and-the-nucleus
#13
REVIEW
Yaru Dong, Takeshi Yoshitomi, Ji-Fan Hu, Jizhe Cui
In animal cells, mitochondria are the primary powerhouses and metabolic factories. They also contain genomes and can produce mitochondrial-specific nucleic acids and proteins. To maintain homeostasis of the entire cell, an intense cross-talk between mitochondria and the nucleus, mediated by encoded noncoding RNAs (ncRNAs), as well as proteins, is required. Long ncRNAs (lncRNAs) contain characteristic structures, and they are involved in the regulation of almost every stage of gene expression, as well as being implicated in a variety of disease states, such as cancer...
August 23, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28826699/major-surgery-diminishes-systemic-arginine-availability-and-suppresses-nitric-oxide-response-to-feeding-in-patients-with-early-stage-breast-cancer
#14
Mariëlle P K J Engelen, V Suzanne Klimberg, Arianna Allasia, Nicolaas E P Deutz
BACKGROUND & AIMS: Plasma arginine (ARG) levels are reduced in breast cancer, suggesting diminished systemic ARG availability. ARG and its product nitric oxide (NO) are important in early postoperative recovery due to its roles in immune function and wound healing. It remains unclear whether major surgery further diminishes systemic ARG availability due to enhanced ARG catabolism and/or insufficient endogenous ARG synthesis negatively affecting NO synthesis in patients with early stage breast cancer...
August 5, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28826492/environmental-cystine-drives-glutamine-anaplerosis-and-sensitizes-cancer-cells-to-glutaminase-inhibition
#15
Alexander Muir, Laura V Danai, Dan Y Gui, Chiara Y Waingarten, Caroline A Lewis, Matthew G Vander Heiden
Many mammalian cancer cell lines depend on glutamine as a major tri-carboxylic acid (TCA) cycle anaplerotic substrate to support proliferation. However, some cell lines that depend on glutamine anaplerosis in culture rely less on glutamine catabolism to proliferate in vivo. We sought to understand the environmental differences that cause differential dependence on glutamine for anaplerosis. We find that cells cultured in adult bovine serum, which better reflects nutrients available to cells in vivo, exhibit decreased glutamine catabolism and reduced reliance on glutamine anaplerosis compared to cells cultured in standard tissue culture conditions...
August 15, 2017: ELife
https://www.readbyqxmd.com/read/28814091/the-effect-of-vitamin-d-on-mcf-7-breast-cancer-cell-metabolism
#16
B Saracligil, B Ozturk, A Unlu, S Abusoglu, G Tekin
The role of vitamin D in calcium absorption and bone health is known. The studies revealed that vitamin D modulates breast cancer cell growth and it is also associated with a reduced breast cancer risk. The primary objective of this study was to highlight the metabolic effect of Vitamin D on MCF-7 breast cancer cell line. For that purpose, we checked the apoptosis, energy, amino-acid and acylcarnitine levels in cancer cells, that the study propose, that 1α, 25(OH)2D3 could inhibit cell growth in a dose and time dependent manner...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28813676/pharmacologic-or-genetic-targeting-of-glutamine-synthetase-skews-macrophages-toward-an-m1-like-phenotype-and-inhibits-tumor-metastasis
#17
Erika M Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, Douglas C Hooper, Wouter H Lamers, Bart Ghesquière, Daniel W McVicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna
Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28811348/a-critical-role-of-glutamine-and-asparagine-%C3%AE-nitrogen-in-nucleotide-biosynthesis-in-cancer-cells-hijacked-by-an-oncogenic-virus
#18
Ying Zhu, Tingting Li, Suzane Ramos da Silva, Jae-Jin Lee, Chun Lu, Hyungjin Eoh, Jae U Jung, Shou-Jiang Gao
While glutamine is a nonessential amino acid that can be synthesized from glucose, some cancer cells primarily depend on glutamine for their growth, proliferation, and survival. Numerous types of cancer also depend on asparagine for cell proliferation. The underlying mechanisms of the glutamine and asparagine requirement in cancer cells in different contexts remain unclear. In this study, we show that the oncogenic virus Kaposi's sarcoma-associated herpesvirus (KSHV) accelerates the glutamine metabolism of glucose-independent proliferation of cancer cells by upregulating the expression of numerous critical enzymes, including glutaminase 2 (GLS2), glutamate dehydrogenase 1 (GLUD1), and glutamic-oxaloacetic transaminase 2 (GOT2), to support cell proliferation...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28809118/glucose-limitation-alters-glutamine-metabolism-in-muc1-overexpressing-pancreatic-cancer-cells
#19
Teklab Gebregiworgis, Vinee Purohit, Surendra K Shukla, Saber Tadros, Nina V Chaika, Jaime Abrego, Scott E Mulder, Venugopal Gunda, Pankaj K Singh, Robert Powers
Pancreatic cancer cells overexpressing Mucin 1 (MUC1) rely on aerobic glycolysis and, correspondingly, are dependent on glucose for survival. Our NMR metabolomics comparative analysis of control (S2-013.Neo) and MUC1-overexpressing (S2-013.MUC1) cells demonstrates that MUC1 reprograms glutamine metabolism upon glucose limitation. The observed alteration in glutamine metabolism under glucose limitation was accompanied by a relative decrease in the proliferation of MUC1-overexpressing cells compared with steady-state conditions...
August 30, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28808255/critical-role-for-arginase-2-in-obesity-associated-pancreatic-cancer
#20
Tamara Zaytouni, Pei-Yun Tsai, Daniel S Hitchcock, Cory D DuBois, Elizaveta Freinkman, Lin Lin, Vicente Morales-Oyarvide, Patrick J Lenehan, Brian M Wolpin, Mari Mino-Kenudson, Eduardo M Torres, Nicholas Stylopoulos, Clary B Clish, Nada Y Kalaany
Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDA). Despite recent identification of metabolic alterations in this lethal malignancy, the metabolic dependencies of obesity-associated PDA remain unknown. Here we show that obesity-driven PDA exhibits accelerated growth and a striking transcriptional enrichment for pathways regulating nitrogen metabolism. We find that the mitochondrial form of arginase (ARG2), which hydrolyzes arginine into ornithine and urea, is induced upon obesity, and silencing or loss of ARG2 markedly suppresses PDA...
August 14, 2017: Nature Communications
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