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Warburg effect

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https://www.readbyqxmd.com/read/29030545/fructose-1-6-bisphosphate-couples-glycolytic-flux-to-activation-of-ras
#1
Ken Peeters, Frederik Van Leemputte, Baptiste Fischer, Beatriz M Bonini, Hector Quezada, Maksym Tsytlonok, Dorien Haesen, Ward Vanthienen, Nuno Bernardes, Carmen Bravo Gonzalez-Blas, Veerle Janssens, Peter Tompa, Wim Versées, Johan M Thevelein
Yeast and cancer cells share the unusual characteristic of favoring fermentation of sugar over respiration. We now reveal an evolutionary conserved mechanism linking fermentation to activation of Ras, a major regulator of cell proliferation in yeast and mammalian cells, and prime proto-oncogene product. A yeast mutant (tps1∆) with overactive influx of glucose into glycolysis and hyperaccumulation of Fru1,6bisP, shows hyperactivation of Ras, which causes its glucose growth defect by triggering apoptosis. Fru1,6bisP is a potent activator of Ras in permeabilized yeast cells, likely acting through Cdc25...
October 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29029484/ybx1-promotes-tumor-growth-by-elevating-glycolysis-in-human-bladder-cancer
#2
Liuyu Xu, Hongyun Li, Longchao Wu, Shiming Huang
Aerobic glycolysis, also known as Warburg effect, is a key hallmark of cancers. The Y-box-binding protein 1 (YBX1) is a well-known oncoprotein implicated in multiple malignant phenotypes of cancers. Meanwhile, little is known about the oncogenic functions and mechanisms of YBX1 in bladder cancer. Based on gene set enrichment analysis (GSEA) of TCGA RNAseq data, we find that YBX1 was profoundly involved in the glycolysis part of glucose metabolism. Loss- and gain-of-function studies show that YBX1 can enhance glycolysis as revealed by expression of glycolytic enzymes, glucose uptake, lactate secretion and extracellular acidification rate (ECAR)...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29028346/influence-of-hofmeister-i-on-tuning-optoelectronic-properties-of-ampholytic-polythiophene-by-varying-ph-and-conjugating-with-rna
#3
Radhakanta Ghosh, Dhruba P Chatterjee, Sujoy Das, Titas Kumar Mukhopadhyay, Ayan Datta, Arun K Nandi
A significant tuning of optoelectronic properties of polythiophene (PT) chains due to Hofmeister iodide (I-) ion is demonstrated in ampholytic polythiophene [polythiophene-g-poly{(N,N,N-trimethylamino iodide)ethyl methacrylate-co-methacrylic acid}, APT] at different pH. In acidic medium, the absorption and emission signals of PT chromophore exhibit appreciable blue shift in presence of I- as counter anion only. The co-operative effect of undissociated -COOH and quaternary ammonium groups immobilize I- near apolar PT chain causing threading of grafted chains and hence twisting of the backbone attributing to the blue shift...
October 13, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29026202/loss-of-abhd5-promotes-the-aggressiveness-of-prostate-cancer-cells
#4
Guohua Chen, Guoli Zhou, Siddhesh Aras, Zhenhui He, Stephanie Lucas, Izabela Podgorski, Wael Skar, James G Granneman, Jian Wang
The accumulation of neutral lipids in intracellular lipid droplets has been associated with the formation and progression of many cancers, including prostate cancer (PCa). Alpha-beta Hydrolase Domain Containing 5 (ABHD5) is a key regulator of intracellular neutral lipids that has been recently identified as a tumor suppressor in colorectal cancer, yet its potential role in PCa has not been investigated. Through mining publicly accessible PCa gene expression datasets, we found that ABHD5 gene expression is markedly decreased in metastatic castration-resistant PCa (mCRPC) samples...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29024608/erastin-like-anti-warburg-agents-prevent-mitochondrial-depolarization-induced-by-free-tubulin-and-decrease-lactate-formation-in-cancer-cells
#5
David N DeHart, John J Lemasters, Eduardo N Maldonado
In Warburg metabolism, suppression of mitochondrial metabolism contributes to a low cytosolic ATP/ADP ratio favoring enhanced aerobic glycolysis. Flux of metabolites across the mitochondrial outer membrane occurs through voltage-dependent anion channels (VDAC). In cancer cells, free dimeric tubulin induces VDAC closure and dynamically regulates mitochondrial membrane potential (ΔΨ). Erastin, a small molecule that binds to VDAC, antagonizes the inhibitory effect of tubulin on VDAC and hyperpolarizes mitochondria in intact cells...
September 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28985623/maintenance-of-cellular-respiration-indicates-drug-resistance-in-acute-myeloid-leukemia
#6
Katharina Henkenius, Brandon H Greene, Christina Barckhausen, Raimo Hartmann, Melanie Märken, Tom Kaiser, Miriam Rehberger, Stephan K Metzelder, Wolfgang J Parak, Andreas Neubauer, Cornelia Brendel, Elisabeth Mack
Primary resistance to induction therapy is an unsolved clinical problem in acute myeloid leukemia (AML). Here we investigated drug resistance in AML at the level of cellular metabolism in order to identify early predictors of therapeutic response. Using extracellular flux analysis, we compared metabolic drug responses in AML cell lines sensitive or resistant to cytarabine or sorafenib after 24h of drug treatment to a small cell lung cancer (SCLC) cell line exposed to etoposide. Only drug-resistant AML cells maintained oxidative metabolism upon drug exposure while SCLC cells displayed an overall metabolic shift towards glycolysis, i...
September 28, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28983605/ldha-promotes-tumor-metastasis-by-facilitating-epithelial%C3%A2-mesenchymal-transition-in-renal-cell-carcinoma
#7
Juping Zhao, Xin Huang, Zhaoping Xu, Jun Dai, Hongchao He, Yu Zhu, Haofei Wang
Previous studies have indicated that high expression of lactate dehydrogenase A (LDHA) exists in many human cancers. Recently, several reports showed that silencing or inhibition of LDHA could suppress metastasis of human cancer including renal cell carcinoma (RCC). However, the mechanism remains unknown. The role of LDHA in RCC migration and invasion was investigated using immunohistochemistry, western blotting, Transwell and scratch assays, and in vivo experiment. The influence of LDHA on the Warburg effect was also investigated by LDHA activity and lactate production assay...
September 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28981396/cancer-specific-energy-metabolism-in-rhabdomyosarcoma-cells-is-regulated-by-microrna
#8
Nobuhiko Sugito, Kohei Taniguchi, Yuki Kuranaga, Maki Ohishi, Tomoyoshi Soga, Yuko Ito, Mitsuru Miyachi, Ken Kikuchi, Hajime Hosoi, Yukihiro Akao
Rhabdomyosarcoma (RMS) is a soft tissue sarcoma and is most frequently found in children. In RMS, there are two major subtypes, that is, embryonal RMS and alveolar RMS (ARMS). ARMS has exclusively the worse prognosis and is caused by formation of the chimeric PAX3-FOXO1 gene. Regarding cancer, the Warburg effect is known as a feature of cancer-specific metabolism. Polypyrimidine tract-binding protein 1 (PTBP1), a splicer of pyruvate kinase muscle (PKM) mRNA, is a positive regulator of cancer-specific energy metabolism...
October 5, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28980925/mir-214-modulates-cisplatin-sensitivity-of-osteosarcoma-cells-through-regulation-of-anaerobic-glycolysis
#9
Y-D Song, D-D Li, Y Guan, Y-L Wang, J Zheng
Osteosarcoma is the most frequent primary bone tumor originating from adolescents and young adults. Despite improvements in the chemo- or radio- therapy of osteosarcoma patients, survival rate has not increased and drug resistance becomes a major factor that limits the effectiveness. Therefore, investigation of new treatment modalities is urgently required to optimize therapeutic options. Our previous study described an oncogenic role of miR-214 through promotion of osteosarcoma cells proliferation. In this study, we report miR-214 contributes to cisplatin resistance in osteosarcoma cells...
September 30, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28978464/ampk-maintains-cellular-metabolic-homeostasis-through-regulation-of-mitochondrial-reactive-oxygen-species
#10
Rebecca C Rabinovitch, Bozena Samborska, Brandon Faubert, Eric H Ma, Simon-Pierre Gravel, Sylvia Andrzejewski, Thomas C Raissi, Arnim Pause, Julie St-Pierre, Russell G Jones
Reactive oxygen species (ROS) are continuously produced as a by-product of mitochondrial metabolism and eliminated via antioxidant systems. Regulation of mitochondrially produced ROS is required for proper cellular function, adaptation to metabolic stress, and bypassing cellular senescence. Here, we report non-canonical regulation of the cellular energy sensor AMP-activated protein kinase (AMPK) by mitochondrial ROS (mROS) that functions to maintain cellular metabolic homeostasis. We demonstrate that mitochondrial ROS are a physiological activator of AMPK and that AMPK activation triggers a PGC-1α-dependent antioxidant response that limits mitochondrial ROS production...
October 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28970966/increased-utilization-of-fructose-has-a-positive-effect-on-the-development-of-breast-cancer
#11
Xiajing Fan, Hongru Liu, Miao Liu, Yuanyuan Wang, Li Qiu, Yanfen Cui
Rapid proliferation and Warburg effect make cancer cells consume plenty of glucose, which induces a low glucose micro-environment within the tumor. Up to date, how cancer cells keep proliferating in the condition of glucose insufficiency still remains to be explored. Recent studies have revealed a close correlation between excessive fructose consumption and breast cancer genesis and progression, but there is no convincing evidence showing that fructose could directly promote breast cancer development. Herein, we found that fructose, not amino acids, could functionally replace glucose to support proliferation of breast cancer cells...
2017: PeerJ
https://www.readbyqxmd.com/read/28966808/aging-metabolism-and-cancer-development-from-peto-s-paradox-to-the-warburg-effect
#12
REVIEW
Tia R Tidwell, Kjetil Søreide, Hanne R Hagland
Medical advances made over the last century have increased our lifespan, but age-related diseases are a fundamental health burden worldwide. Aging is therefore a major risk factor for cardiovascular disease, cancer, diabetes, obesity, and neurodegenerative diseases, all increasing in prevalence. However, huge inter-individual variations in aging and disease risk exist, which cannot be explained by chronological age, but rather physiological age decline initiated even at young age due to lifestyle. At the heart of this lies the metabolic system and how this is regulated in each individual...
October 2017: Aging and Disease
https://www.readbyqxmd.com/read/28957320/a-metabolic-core-model-elucidates-how-enhanced-utilization-of-glucose-and-glutamine-with-enhanced-glutamine-dependent-lactate-production-promotes-cancer-cell-growth-the-warburq-effect
#13
Chiara Damiani, Riccardo Colombo, Daniela Gaglio, Fabrizia Mastroianni, Dario Pescini, Hans Victor Westerhoff, Giancarlo Mauri, Marco Vanoni, Lilia Alberghina
Cancer cells share several metabolic traits, including aerobic production of lactate from glucose (Warburg effect), extensive glutamine utilization and impaired mitochondrial electron flow. It is still unclear how these metabolic rearrangements, which may involve different molecular events in different cells, contribute to a selective advantage for cancer cell proliferation. To ascertain which metabolic pathways are used to convert glucose and glutamine to balanced energy and biomass production, we performed systematic constraint-based simulations of a model of human central metabolism...
September 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28955240/morin-inhibits-proliferation-of-sw480-colorectal-cancer-cells-by-inducing-apoptosis-mediated-by-reactive-oxygen-species-formation-and-uncoupling-of-warburg-effect
#14
Thomas Sithara, K B Arun, H P Syama, T R Reshmitha, P Nisha
The study under investigation focuses on in vitro antiproliferative efficacy of the flavonoid morin and the mechanisms by which it inhibits the growth of colon cancer using SW480 colon cancer cells with emphasis on Warburg effect. It was found that the cell proliferation was significantly inhibited by morin in a dose and time dependent manner. Morin induced apoptosis that was correlated with increased levels of reactive oxygen species formation and loss of mitochondrial membrane potential of the cells. In addition, an increase in cleaved PARP, cleaved caspase 3, cleaved caspase 8, cleaved caspase 9 and Bax as well as a decrease in Bcl 2 was observed, indicating morin is inducing both intrinsic as well as extrinsic pathway of apoptosis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28944767/reply-to-comment-on-the-cancer-warburg-effect-may-be-a-testable-example-of-the-minimum-entropy-production-rate-principle
#15
Bartolome Sabater, Dolores Marín
We point that the minimum rate theorem [3] refers to internal entropy production (ΔSi), here calculated for the chemical reaction in the open cell system. We also point that In the steady-state open system the constant supply of glucose makes equivalent the minimum rate of entropy production per unit of time to the minimum rate of production of entropy per mole of glucose.
September 25, 2017: Physical Biology
https://www.readbyqxmd.com/read/28944760/comment-on-the-cancer-warburg-effect-may-be-a-testable-example-of-the-minimum-entropy-production-rate-principle
#16
Mostafa Sadeghi Ghuchani
Marín and Sabater have estimated the entropy production of cancer cells and compared it to that of normal cells. They estimated that cancer cells produce 10 percent less entropy per mole of glucose in comparison to normal cells and concluded that it may accomplish the minimum entropy production theorem of Prigogine. However, according to previously published papers, it seems that there are two errors both in the method of estimation and conclusion. .
September 25, 2017: Physical Biology
https://www.readbyqxmd.com/read/28938520/galangin-suppresses-hepatocellular-carcinoma-cell-proliferation-by-reversing-the-warburg-effect
#17
Yajun Wang, Biyun Lin, Huimin Li, Liubo Lan, Huajun Yu, Shang Wu, Jun Wu, Haitao Zhang
Hepatocellular carcinoma (HCC) is the sixth most common cancer. The Warburg effect is an important way by which HCC adapts to a hypoxic environment. The aim of the present study was to determine whether and how galangin reverses the Warburg effect in HCC cells. We treated three HCC cell lines, HepG2, Hep3B and PLC/PRF/5 with galangin for 24h, respectively. Cell proliferation was measured with MTT assay. Glucose uptake, lactate production and the oxygen consumption were measured. Pyruvate kinase activities were detected by measuring the consumption of NADH, and glycolytic pathway-related proteins were measured by Western blotting...
September 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28933733/melatonin-decreases-glucose-metabolism-in-prostate-cancer-cells-a-13-c-stable-isotope-resolved-metabolomic-study
#18
David Hevia, Pedro Gonzalez-Menendez, Mario Fernandez-Fernandez, Sergio Cueto, Pablo Rodriguez-Gonzalez, Jose I Garcia-Alonso, Juan C Mayo, Rosa M Sainz
The pineal neuroindole melatonin exerts an exceptional variety of systemic functions. Some of them are exerted through its specific membrane receptors type 1 and type 2 (MT1 and MT2) while others are mediated by receptor-independent mechanisms. A potential transport of melatonin through facilitative glucose transporters (GLUT/SLC2A) was proposed in prostate cancer cells. The prostate cells have a particular metabolism that changes during tumor progression. During the first steps of carcinogenesis, oxidative phosphorylation is reactivated while the switch to the "Warburg effect" only occurs in advanced tumors and in the metastatic stage...
July 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28927903/linker-structure-activity-relationships-in-fluorodeoxyglucose-chlorambucil-conjugates-for-tumor-targeted-chemotherapy
#19
Mostafa El Hilali, Bastien Reux, Eric Debiton, Fernand Leal, Marie-Josephe Galmier, Magali Vivier, Jean-Michel Chezal, Elisabeth Miot-Noirault, Pascal Coudert, Valérie Weber
Nitrogen mustards, such as chlorambucil (CLB), can cause adverse side-effects due to ubiquitous distribution in non-target organs. To minimize this toxicity, strategies of tumor-targeting drug delivery have been developed, where a cytotoxic warhead is linked to a tumor-cell-specific small ligand. Malignant cells exhibit marked glucose avidity and an accelerated metabolism by aerobic glycolysis, known as the Warburg effect, and recognized as a hallmark of cancer. A targeting approach exploiting the Warburg effect by conjugation of CLB to 2-fluoro-2-deoxyglucose (FDG) was previously reported and identified two peracetylated glucoconjugates 2 and 3 with promising antitumor activities in vivo...
August 30, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28922380/the-warburg-effect-as-an-adaptation-of-cancer-cells-to-rapid-fluctuations-in-energy-demand
#20
Tamir Epstein, Robert A Gatenby, Joel S Brown
To maintain optimal fitness, a cell must balance the risk of inadequate energy reserve for response to a potentially fatal perturbation against the long-term cost of maintaining high concentrations of ATP to meet occasional spikes in demand. Here we apply a game theoretic approach to address the dynamics of energy production and expenditure in eukaryotic cells. Conventionally, glucose metabolism is viewed as a function of oxygen concentrations in which the more efficient oxidation of glucose to CO2 and H2O produces all or nearly all ATP except under hypoxic conditions when less efficient (2 ATP/ glucose vs...
2017: PloS One
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