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https://www.readbyqxmd.com/read/28938520/galangin-suppresses-hepatocellular-carcinoma-cell-proliferation-by-reversing-the-warburg-effect
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/28918937/a-predictive-model-for-selective-targeting-of-the-warburg-effect-through-gapdh-inhibition-with-a-natural-product
#5
Maria V Liberti, Ziwei Dai, Suzanne E Wardell, Joshua A Baccile, Xiaojing Liu, Xia Gao, Robert Baldi, Mahya Mehrmohamadi, Marc O Johnson, Neel S Madhukar, Alexander A Shestov, Iok I Christine Chio, Olivier Elemento, Jeffrey C Rathmell, Frank C Schroeder, Donald P McDonnell, Jason W Locasale
Targeted cancer therapies that use genetics are successful, but principles for selectively targeting tumor metabolism that is also dependent on the environment remain unknown. We now show that differences in rate-controlling enzymes during the Warburg effect (WE), the most prominent hallmark of cancer cell metabolism, can be used to predict a response to targeting glucose metabolism. We establish a natural product, koningic acid (KA), to be a selective inhibitor of GAPDH, an enzyme we characterize to have differential control properties over metabolism during the WE...
September 8, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28915713/the-reverse-warburg-effect-is-likely-to-be-an-achilles-heel-of-cancer-that-can-be-exploited-for-cancer-therapy
#6
REVIEW
Yaojie Fu, Shanshan Liu, Shanghelin Yin, Weihong Niu, Wei Xiong, Ming Tan, Guiyuan Li, Ming Zhou
Although survival outcomes of cancer patients have been improved dramatically via conventional chemotherapy and targeted therapy over the last decades, there are still some tough clinical challenges that badly needs to be overcome, such as anticancer drug resistance, inevitable recurrences, cancer progression and metastasis. Simultaneously, accumulated evidence demonstrates that aberrant glucose metabolism termed 'the Warburg effect' in cancer cell is closely associated with malignant phenotypes. In 2009, a novel 'two-compartment metabolic coupling' model, also named 'the reverse Warburg effect', was proposed and attracted lots of attention...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915665/the-ketogenic-diet-is-not-feasible-as-a-therapy-in-a-cd-1-nu-nu-mouse-model-of-renal-cell-carcinoma-with-features-of-stauffer-s-syndrome
#7
Silvia Vidali, Sepideh Aminzadeh-Gohari, René Günther Feichtinger, Renaud Vatrinet, Andreas Koller, Felix Locker, Tricia Rutherford, Maura O'Donnell, Andrea Stöger-Kleiber, Bridget Lambert, Thomas Klaus Felder, Wolfgang Sperl, Barbara Kofler
The ketogenic diet (KD), a high-fat low-carbohydrate diet, has shown some efficacy in the treatment of certain types of tumors such as brain tumors and neuroblastoma. These tumors are characterized by the Warburg effect. Because renal cell carcinoma (RCC) presents similar energetic features as neuroblastoma, KD might also be effective in the treatment of RCC. To test this, we established xenografts with RCC 786-O cells in CD-1 nu/nu mice and then randomized them to a control diet or to KDs with different triglyceride contents...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915394/overcoming-the-warburg-effect-is-it-the-key-to-survival-in-sepsis
#8
REVIEW
David Bar-Or, Matthew Carrick, Allen Tanner, Mark J Lieser, Leonard T Rael, Edward Brody
Sepsis is a leading cause of mortality in the U.S. and Europe. Sepsis and septic shock are the results of severe metabolic abnormalities following infection. Aerobic glycolysis (the Warburg Effect) is as much a hallmark of sepsis as it is of cancer. Warburg observed that cancer cells generated energy through glycolysis (generation of ATP through degradation of glucose, usually associated with anaerobic conditions) rather than through oxidative phosphorylation (generation of ATP through the mitochondrial inner membrane via the tricarboxylic acid cycle, usually associated with aerobic conditions)...
September 8, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28914667/metabolic-regulation-of-macrophages-in-tumor-microenvironment
#9
Jaehong Kim, Jong-Sup Bae
PURPOSE OF REVIEW: Insight into the metabolic changes in cancer has become so important that cancer is regarded as a disease entity full of metabolic implications. We summarize the recent findings pertaining to cancer cell-derived metabolic changes that regulate the function of macrophages to favor cancer cell survival, and the reported approaches to reverse these changes. RECENT FINDINGS: Since the observation and dramatic revitalization of the Warburg effect, metabolic changes were thought to be confined in cancer cells...
September 13, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28903497/downregulation-of-tmem70-in-rat-liver-cells-after-hepatocarcinogen-treatment-related-to-the-warburg-effect-in-hepatocarcinogenesis-producing-gst-p-expressing-proliferative-lesions
#10
Sayaka Mizukami, Yousuke Watanabe, Kota Nakajima, Yasuko Hasegawa-Baba, Meilan Jin, Toshinori Yoshida, Makoto Shibutani
We previously observed downregulation of mitochondrial oxidative phosphorylation-related protein, TMEM70, which is suggestive of disrupted cellular senescence, in GST-P-expressing (+) proliferative lesions from early hepatocarcinogenesis stages in rats. The present study investigated the immunohistochemical relationship between TMEM70 downregulation and cellular metabolic changes in carcinogenic processes, as well as the onset of the liver cell respiratory changes after repeated hepatocarcinogen treatment in rats...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28903423/mitochondria-sustain-store-operated-currents-in-colon-cancer-cells-but-not-in-normal-colonic-cells-reversal-by-non-steroidal-anti-inflammatory-drugs
#11
Miriam Hernández-Morales, Diego Sobradillo, Ruth A Valero, Eva Muñoz, Daniel Ubierna, Mary P Moyer, Lucía Núñez, Carlos Villalobos
Tumor cells undergo a critical remodeling of intracellular Ca(2+) homeostasis that contribute to important cancer hallmarks. Store-operated Ca(2+) entry (SOCE), a Ca(2+) entry pathway modulated by mitochondria, is dramatically enhanced in colon cancer cells. In addition, most cancer cells display the Warburg effect, a metabolic switch from mitochondrial metabolism to glycolysis that provides survival advantages. Accordingly, we investigated mitochondria control of store-operated currents (SOCs) in two cell lines previously selected for representing human normal colonic cells and colon cancer cells...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28900510/egln1-c-myc-induced-lymphoid-specific-helicase-inhibits-ferroptosis-through-lipid-metabolic-gene-expression-changes
#12
Yiqun Jiang, Chao Mao, Rui Yang, Bin Yan, Ying Shi, Xiaoli Liu, Weiwei Lai, Yating Liu, Xiang Wang, Desheng Xiao, Hu Zhou, Yan Cheng, Fenglei Yu, Ya Cao, Shuang Liu, Qin Yan, Yongguang Tao
Ferroptosis is a newly discovered form of non-apoptotic cell death in multiple human diseases. However, the epigenetic mechanisms underlying ferroptosis remain poorly defined. First, we demonstrated that lymphoid-specific helicase (LSH), which is a DNA methylation modifier, interacted with WDR76 to inhibit ferroptosis by activating lipid metabolism-associated genes, including GLUT1, and ferroptosis related genes SCD1 and FADS2, in turn, involved in the Warburg effect. WDR76 targeted these genes expression in dependent manner of LSH and chromatin modification in DNA methylation and histone modification...
2017: Theranostics
https://www.readbyqxmd.com/read/28894242/complementary-acsl-isoforms-contribute-to-a-non-warburg-advantageous-energetic-status-characterizing-invasive-colon-cancer-cells
#13
Ruth Sánchez-Martínez, Silvia Cruz-Gil, María Soledad García-Álvarez, Guillermo Reglero, Ana Ramírez de Molina
Metabolic reprogramming is one of cancer hallmarks. Here, we focus on functional differences and individual contribution of acyl coA synthetases (ACSL) isoforms to the previously described ACSL/stearoyl-CoA desaturase (ACSL1/ACSL4/SCD) metabolic network causing invasion and poor prognosis in colorectal cancer (CRC). ACSL4 fuels proliferation and migration accompanied by a more glycolytic phenotype. Conversely, ACSL1 stimulates invasion displaying a lower basal respiratory rate. Acylcarnitines elevation, polyunsaturated fatty acids (PUFA) lower levels, and monounsaturated fatty acids (MUFA) upregulation characterize the individual overexpression of ACSL1, ACSL4 and SCD, respectively...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28887057/ppar%C3%AE-agonists-potential-treatments-for-exudative-age-related-macular-degeneration
#14
REVIEW
Alexandre Vallée, Yves Lecarpentier, Rémy Guillevin, Jean-Noël Vallée
Choroidal neovascularization (CNV) characterizes the progression of exudative age-related macular degeneration (AMD) with the deterioration in the central vision. Vascular inflammation, and overproduction of inflammatory cytokines, growth factors and aberrant endothelial cell migration, initiate defective blood vessel proliferation in exudative AMD. CNV formation is initiated by the interplay between inflammation, the hallmark of exudative AMD, and the activation of WNT/β-catenin pathway. Upregulation of WNT/β-catenin pathway involves activation of PI3K/Akt pathway and then the Warburg effect to produce lactate...
September 5, 2017: Life Sciences
https://www.readbyqxmd.com/read/28881704/chaperone-mediated-autophagy-substrate-proteins-in-cancer
#15
REVIEW
Ying Tang, Xiong-Wen Wang, Zhan-Hua Liu, Yun-Ming Sun, Yu-Xin Tang, Dai-Han Zhou
All intracellular proteins undergo continuous synthesis and degradation. Chaperone-mediated autophagy (CMA) is necessary to maintain cellular homeostasis through turnover of cytosolic proteins (substrate proteins). This degradation involves a series of substrate proteins including both cancer promoters and suppressors. Since activating or inhibiting CMA pathway to treat cancer is still debated, targeting to the CMA substrate proteins provides a novel direction. We summarize the cancer-associated substrate proteins which are degraded by CMA...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28875197/analysis-of-warburg-s-impedance-and-its-equivalent-electric-circuits
#16
G Barbero, I Lelidis
The derivation of Warburg's impedance is revisited and critically analyzed. We show that the original derivation where the electric current is assumed to be due only to the diffusion of ions, as proposed by Warburg, raises some fundamental questions. The roles of the drift current, in the absence of which the equilibrium is never reached in the dc case, and of the displacement current, which is important even in the low frequency region where the Warburg's impedance appears, are discussed. Finally, the utility of models based on equivalent electric circuits, ladder networks, or transmission lines in the analysis of impedance spectroscopy data is investigated...
September 20, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28868241/targeting-cancer-with-tumor-specific-therapeutic-strategies-metabolic-reprogramming-beyond-the-warburg-effect
#17
COMMENT
Paul Grippo, Ajay V Maker
No abstract text is available yet for this article.
May 2017: Translational Cancer Research
https://www.readbyqxmd.com/read/28867389/legionella-pneumophila-modulates-mitochondrial-dynamics-to-trigger-metabolic-repurposing-of-infected-macrophages
#18
Pedro Escoll, Ok-Ryul Song, Flávia Viana, Bernhard Steiner, Thibault Lagache, Jean-Christophe Olivo-Marin, Francis Impens, Priscille Brodin, Hubert Hilbi, Carmen Buchrieser
The intracellular bacteria Legionella pneumophila encodes a type IV secretion system (T4SS) that injects effector proteins into macrophages in order to establish and replicate within the Legionella-containing vacuole (LCV). Once generated, the LCV interacts with mitochondria through unclear mechanisms. We show that Legionella uses both T4SS-independent and T4SS-dependent mechanisms to respectively interact with mitochondria and induce mitochondrial fragmentation that ultimately alters mitochondrial metabolism...
September 13, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28859278/the-transcriptome-of-the-endometrium-and-placenta-is-associated-with-pregnancy-development-but-not-lactation-status-in-dairy-cows
#19
Stephen G Moore, Matthew S McCabe, Jacob C Green, Emily M Newsom, Matthew C Lucy
Infertility in lactating dairy cows is explained partially by the metabolic state associated with high milk production. The hypothesis was that lactating and nonlactating cows would differ in endometrial and placental transcriptomes during early pregnancy (day 28 to 42) and this difference would explain the predisposition for lactating cows to have embryonic loss at that time. Cows were either milked or not milked after calving. Reproductive [endometrium (caruncular and intercaruncular) and placenta] and liver tissues were collected on day 28, 35, and 42 of pregnancy...
July 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28857035/two-common-variants-of-human-papillomavirus-type-16-e6-differentially-deregulate-sugar-metabolism-and-hypoxia-signalling-in-permissive-human-keratinocytes
#20
Sean Cuninghame, Robert Jackson, Simon J Lees, Ingeborg Zehbe
Human papillomavirus type 16 (HPV16) is responsible for most cancers attributable to HPV infection and naturally occurring variants of the HPV16 E6 oncoprotein predispose individuals to varying risk for developing cancer. Population studies by us and others have demonstrated that the common Asian-American E6 (AAE6) variant is a higher risk factor for cervical cancer than the E6 of another common variant, the European prototype (EPE6). However, a complete understanding of the molecular processes fundamental to these epidemiological findings is still lacking...
September 2017: Journal of General Virology
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