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https://www.readbyqxmd.com/read/29788892/inhibition-of-glycolysis-and-glutaminolysis-emerging-drug-discovery-approach-to-combat-cancer
#1
Nicholas S Akins, Tanner C Nielson, Hoang V Le
Cancer cells have a very different metabolism from that of normal cells from which they are derived. Their metabolism is elevated, which allows them to sustain higher proliferative rate and resist some cell death signals. This phenomenon, known as the "Warburg effect", has become the focus of intensive efforts in the discovery of new therapeutic targets and new cancer drugs. Both glycolysis and glutaminolysis pathways are enhanced in cancer cells. While glycolysis is enhanced to satisfy the increasing energy demand of cancer cells, glutaminolysis is enhanced to provide biosynthetic precursors for cancer cells...
May 22, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29784881/structural-basis-for-adp-dependent-glucokinase-inhibition-by-8-bromo-substituted-adenosine-nucleotide
#2
Przemyslaw Grudnik, Marcin M Kaminski, Krzysztof P Rembacz, Katarzyna Kuska, Mariusz Madej, Jan Potempa, Maciej Dawidowski, Grzegorz Dubin
In higher eukaryotes, several ATP-utilizing enzymes known as hexokinases activate glucose in the glycolysis pathway by phosphorylation to glucose-6-phosphate. In contrast to canonical hexokinases which use ATP, ADP-dependent glucokinase (ADPGK) catalyzes non-canonical phosphorylation of glucose to glucose-6-phosphate using ADP as a phosphate donor. Initially discovered in Archaea, the human homolog of ADPGK was described only recently. ADPGK's involvement in modified bioenergetics of activated T cells has been postulated and elevated ADPGK expression has been reported in various cancer tissues...
May 21, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29778741/changes-in-lipid-protein-and-carbohydrate-metabolism-in-spodoptera-exigua-larvae-associated-with-infection-by-heliothis-virescens-ascovirus-3h
#3
Zi-Qi Li, Huan Yu, Guo-Hua Huang
Spodoptera exigua (Lepidoptera: Noctuidae) larvae were used to analyze the regulation of lipid, protein and carbohydrate metabolism in host larvae infected with the Heliothis virescens ascovirus 3h (HvAV-3h). Using histological sections, significant pathological changes were found in the fat bodies of infected larvae from 24 h to 72 h post-infection (hpi). The lipid and protein contents of the infected larvae were significantly higher than those of the uninfected larvae, while the carbohydrate content of the infected larvae was significantly lower than that of the mock-infected larvae...
May 17, 2018: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/29777095/butein-inhibited-in-vitro-hexokinase-2-mediated-tumor-glycolysis-in-hepatocellular-carcinoma-by-blocking-epidermal-growth-factor-receptor-egfr
#4
Weirong Liao, Jingtian Liu, Dawei Zhang, Wenhai Huang, Runhao Chen
BACKGROUND Anaerobic glycolysis is an important physiological process of all cancer cells. Butein has been reported to demonstrate substantial antitumor activities in various cancers. However, the effect of butein on tumor glycolysis remains unclear. In this study, the effect of butein on tumor glycolysis and the underlying mechanism were investigated in hepatocellular carcinoma (HCC). MATERIAL AND METHODS Cell proliferation assay and anchorage-independent growth assay were carried out to evaluate the antitumor activities of butein in vitro...
May 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29764240/ferrous-glycinate-regulates-cell-energy-metabolism-by-restricting-hypoxia-induced-factor-1%C3%AE-expression-in-human-a549-cells
#5
Yung-Ting Kuo, Jhong-Huei Jheng, Mei-Chen Lo, Wei-Lu Chen, Shyang-Guang Wang, Horng-Mo Lee
Iron or oxygen regulates the stability of hypoxia inducible factor-1α (HIF-1α). We investigated whether ferrous glycinate would affect HIF-1α accumulation, aerobic glycolysis and mitochondrial energy metabolism in human A549 lung cancer cells. Incubation of A549 cells with ferrous glycinate decreased the protein levels of HIF-1α, which was abrogated by proteosome inhibitor, or prolyl hydroxylase inhibitor. Addition of ferrous glycinate decreased protein levels of glucose transporter-1, hexokinase-2, and lactate dehydrogenase A, and decreased pyruvate dehydrogenase kinase-1 (PDK-1) and pyruvate dehydrogenase (PDH) phosphorylation in A549 cells...
May 15, 2018: Free Radical Research
https://www.readbyqxmd.com/read/29763606/mir-216a-5p-hexokinase-2-axis-regulates-uveal-melanoma-growth-through-modulation-of-warburg-effect
#6
Ying Liu, Yan Huo, Dajiang Wang, Yanhong Tai, Jie Li, Dongbo Pang, Yan Zhang, Wei Zhao, Nan Du, Yifei Huang
Hexokinase-2 (HK2), the initial as well as the rate-limiting step in glycolysis, is overexpressed in many human cancers, and correlates with poor clinical outcomes. Aerobic glycolysis is a hallmark of cancer, and drugs targeting its enzymes, including HK2, are being developed. However, the mechanisms of HK2 inhibition and the physiological significance of the HK2 inhibitors in cancer cells are rarely reported. Here, we show that microRNA-216a-5p (miR-216a-5p) inhibits HK2 expression by directly targeting its 3'-UTR in uveal melanoma cells...
May 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29758413/physcion-8-o-%C3%AE-glucopyranoside-inhibits-clear-cell-renal-cell-carcinoma-bydownregulating-hexokinase-ii-and-inhibiting-glycolysis
#7
Qiang Wang, Yi Yan, Jie Zhang, Peng Guo, Yuqing Xing, Yong Wang, Fawei Qin, Qingyun Zeng
BACKGROUND: Clear-cell renal cell carcinoma (ccRCC) has the highest prevalence, approximately 80%, amongst all RCC cases. Therefore, the development of novel therapeutic agents against ccRCC is imperative. Our previous studies have shown that physcion 8-O-β-glucopyranoside (PG), an anthraquinone extracted from Rumexjaponicus Houtt, exerted an anti-cancer effect in hepatocellular carcinoma cells. The present study was aimed to investigate a possible anti-neoplastic role of PG in ccRCC and the relevant underlying mechanism...
May 11, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29756477/anti-hyperglycemic-and-anti-inflammatory-activities-of-polyphenolic-rich-extract-of-syzygium-cumini-linn-leaves-in-alloxan-induced-diabetic-rats
#8
Basiru O Ajiboye, Oluwafemi A Ojo, Olivia S Akuboh, Okesola M Abiola, Olajumoke Idowu, Aliyu O Amuzat
In this study, anti-hyperglycemic and anti-inflammatory activities of polyphenolic-rich extract of Syzygium cumini leaves in alloxan-induced diabetic rats were determined. Diabetes was induced by a single intraperitoneal injection of alloxan (150 mg/kg body weight) in female Wistar rats. The rats were orally administered with 400 mg/kg free phenol, 400 mg/kg bound phenol, and 5 mg/kg metformin, respectively. On the 14th day of oral administration, the animals were sacrificed, anti-hyperglycemic and anti-inflammatory were assessed...
January 2018: Journal of evidence-based integrative medicine
https://www.readbyqxmd.com/read/29742915/redox-regulation-of-hexokinases
#9
Petr Heneberg
Significance Hexokinases are key enzymes that are responsible for the first reaction of glycolysis, but they also moonlight other cellular processes, including mitochondrial redox signaling regulation. Modulation of hexokinase activity and spatiotemporal location by reactive oxygen and nitrogen species as well as other gasotransmitters serves as the basis for a unique, underexplored method of tight and flexible regulation of these fundamental enzymes. Recent advances Redox modifications of thiols serve as a molecular code that enables the precise and complex regulation of hexokinases...
May 10, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29735421/3-bromopyruvate-reverses-hypoxia-induced-pulmonary-arterial-hypertension-through-inhibiting-glycolysis-in-vitro-and-in-vivo-studies
#10
Fangzheng Chen, Heng Wang, Jiadan Lai, Shujing Cai, Linbo Yuan
BACKGROUND: Pulmonary arterial smooth muscle cell (PASMC) proliferation is vital to pulmonary vascular remodeling in pulmonary arterial hypertension (PAH) pathogenesis, and inhibiting PASMC metabolism could serve as a new possible therapy to reverse the process. 3-Bromopyruvate (3-BrPA) is an effective glycolysis inhibitor with its effect in PAH remains unclear. Our study aims to assess the therapeutic effect of 3-BrPA in PAH rats and investigate the possible mechanism of 3-BrPA in PASMC proliferation and apoptosis...
May 4, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29731929/cigarette-smoking-and-hyperglycaemia-in-diabetic-patients
#11
Mutiara Indah Sari, Nisrina Sari, Dewi Masyithah Darlan, Raka Jati Prasetya
BACKGROUND: The incidence rate of diabetes mellitus has increased throughout the year. Various studies indicate that smoking may affect glucose metabolism and cause hyperglycemia in diabetes mellitus. This study aimed to compare the blood glucose and HbA1c level in diabetic smoking patients and non-smoking diabetic patients. METHODS: This study used the cross-sectional approach. The study population consisted of 30 diabetic smoking patients and 30 non-smoking diabetic patients...
April 15, 2018: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/29725454/shikonin-vitamin-k-3-and-vitamin-k-5-inhibit-multiple-glycolytic-enzymes-in-mcf-7-cells
#12
Jing Chen, Xun Hu, Jingjie Cui
Glycolysis is the most important source of energy for the production of anabolic building blocks in cancer cells. Therefore, glycolytic enzymes are regarded as potential targets for cancer treatment. Previously, naphthaquinones, including shikonin, vitamin K3 and vitamin K5 , have been proven to decrease the rate of glycolysis in cancer cells, which is partly due to suppressed pyruvate kinase activity. In the present study, enzymatic assays were performed using MCF-7 cell lysate in order to screen the profile of glycolytic enzymes in cancer cells inhibited by shikonin, vitamin K3 and vitamin K5 , in addition to pyruvate kinase...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29724730/metabolic-pathways-and-immunometabolism-in-rare-kidney-diseases
#13
Peter C Grayson, Sean Eddy, Jaclyn N Taroni, Yaíma L Lightfoot, Laura Mariani, Hemang Parikh, Maja T Lindenmeyer, Wenjun Ju, Casey S Greene, Brad Godfrey, Clemens D Cohen, Jeffrey Krischer, Matthias Kretzler, Peter A Merkel
OBJECTIVES: To characterise renal tissue metabolic pathway gene expression in different forms of glomerulonephritis. METHODS: Patients with nephrotic syndrome (NS), antineutrophil cytoplasmic antibody-associated vasculitis (AAV), systemic lupus erythematosus (SLE) and healthy living donors (LD) were studied. Clinically indicated renal biopsies were obtained at time of diagnosis and microdissected into glomerular and tubulointerstitial compartments. Microarray-derived differential gene expression of 88 genes representing critical enzymes of metabolic pathways and 25 genes related to immune cell markers was compared between disease groups...
May 3, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29721175/the-decrease-of-glycolytic-enzyme-hexokinase-1-accelerates-tumor-malignancy-via-deregulating-energy-metabolism-but-sensitizes-cancer-cells-to-2-deoxyglucose-inhibition
#14
Po-Lin Tseng, Chih-Wei Chen, Keng-Hsun Hu, Hung-Chi Cheng, Yuan-Ho Lin, Wen-Hui Tsai, Tain-Junn Cheng, Wei-Hsuan Wu, Chin-Wei Yeh, Chin-Chih Lin, Hui-Ju Tsai, Hao-Chun Chang, Jiin-Haur Chuang, Yan-Shen Shan, Wen-Tsan Chang
Malignant tumors often display an aberrant energy metabolism that relies primarily on glycolysis to produce adenosine triphosphate (ATP) the so-called Warburg effect or aerobic glycolysis. Thus, the elucidation of this energetic alteration in malignant tumors is important in the search for more effective therapeutics against malignant cancers, the most deadly human disease. To investigate whether attenuated glycolytic activity modulates tumor progression, the effects of silencing the first and rate-limiting glycolytic enzyme hexokinase (HK) isozymes HK1 and HK2 were examined...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719086/overexpression-of-genes-associated-with-hypoxia-in-cattle-adapted-to-trans-himalayan-region-of-ladakh
#15
Preeti Verma, Ankita Sharma, Monika Sodhi, Kiran Thakur, Vijay Bharti, Prabhat Kumar, Arup Giri, Sahil Kalia, Shelesh Kumar Swami, Manishi Mukesh
Ladakh is an important part of the Trans-Himalayan region located between the Kunlun mountain range in the north and the main Great Himalayas to the south in the state of Jammu and Kashmir of India. The local cattle from Leh and Ladakh region, known as "Ladakhi cattle" is a unique germplasm having excellent adaptation potential to high altitude hypobaric stress. In the present study, an effort was made to evaluate the transcriptional pattern of hypoxia inducing factor-1 (HIF-1) and several of its regulated genes in PBMCs of local Ladakhi cattle, Holstein Frisian crosses, Jersey (exotic) maintained at high altitude region and Sahiwal (Bos indicus) and Karan Fries (cross bred) cattle maintained in tropical environment...
May 2, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29710658/guava-leaf-inhibits-hepatic-gluconeogenesis-and-increases-glycogen-synthesis-via-ampk-acc-signaling-pathways-in-streptozotocin-induced-diabetic-rats
#16
Ramachandran Vinayagam, Muthukumaran Jayachandran, Stephen Sum Man Chung, Baojun Xu
Psidium guajava (PG) is a short shrub or tree cultivated in tropical and subtropical regions around the world. The leaf extract of PG (guava leaf) has been used historically to cure many ailments. However, mechanisms of action of guava leaf in treating diabetes are not fully understood. Effects and underlying mechanisms of guava leaf on gluconeogenesis and glycogenesis in hepatocytes, insulin signaling proteins, liver function markers, and lipid profile in streptozotocin (STZ) injected diabetic Wistar rats were investigated within the current study...
April 24, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29698587/selective-induction-of-cancer-cell-death-by-vdac1-based-peptides-and-their-potential-use-in-cancer-therapy
#17
Anna Shteinfer-Kuzmine, Zohar Amsalem, Tasleem Arif, Alexandra Zooravlov, Varda Shoshan-Barmatz
Mitochondrial VDAC1 mediates cross-talk between the mitochondria and other parts of the cell by transporting anions, cations, ATP, Ca2+ and metabolites, and serves as a key player in apoptosis. As such, VDAC1 is involved in two important hallmarks of cancer development, namely energy and metabolic reprograming and apoptotic cell death evasion. We previously developed cell-penetrating VDAC1-derived peptides that interact with hexokinase (HK), Bcl-2 and Bcl-xL to prevent the anti-apoptotic activities of these proteins and induce cancer cell death, with a focus on leukemia and glioblastoma...
April 26, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29696133/classical-nf-%C3%AE%C2%BAb-metabolically-reprograms-sarcoma-cells-through-regulation-of-hexokinase-2
#18
Priya Londhe, Peter Y Yu, Yuichi Ijiri, Katherine J Ladner, Joelle M Fenger, Cheryl London, Peter J Houghton, Denis C Guttridge
Background: Metabolic reprogramming has emerged as a cancer hallmark, and one of the well-known cancer-associated metabolic alterations is the increase in the rate of glycolysis. Recent reports have shown that both the classical and alternative signaling pathways of nuclear factor κB (NF-κB) play important roles in controlling the metabolic profiles of normal cells and cancer cells. However, how these signaling pathways affect the metabolism of sarcomas, specifically rhabdomyosarcoma (RMS) and osteosarcoma (OS), has not been characterized...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29695690/-overexpression-of-micrornas-mir-9-98-and-199-correlates-with-the-downregulation-of-hk2-expression-in-colorectal-cancer
#19
A V Snezhkina, G S Krasnov, S O Zhikrivetskaya, I Y Karpova, M S Fedorova, K M Nyushko, M M Belyakov, N V Gnuchev, D V Sidorov, B Y Alekseev, N V Melnikova, A V Kudryavtseva
Glycolysis activation is one of the main features of energy metabolism in cancer cells that is associated with the increase in glycolytic enzyme synthesis, primarily, hexokinases (HKs), in many types of tumors. Conversely, in colorectal cancer (CRC) the decrease in the expression of HK2 gene, which encodes one of the key rate-limiting enzyme of glycolysis, was revealed, thus, the study of the mechanisms of its inhibition in CRC is of particular interest. To search for potential microRNAs, inhibiting the expression of HK2 in CRC, we have performed the analysis of data from "The Cancer Genome Atlas" (TCGA) and five microRNA-mRNA target interaction databases (TargetScan, DIANA microT, mirSVR (miRanda), PicTar, and miRTarBase) using original CrossHub software...
March 2018: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/29684851/mitochondrial-dna-content-reduction-induces-aerobic-glycolysis-and-reversible-resistance-to-drug-induced-apoptosis-in-sw480-colorectal-cancer-cells
#20
Jing-Jing Mou, Jin Peng, Ying-Ying Shi, Na Li, You Wang, Yuan Ke, Yun-Feng Zhou, Fu-Xiang Zhou
Mutations and reductions in mitochondrial DNA (mtDNA), which are frequent in human tumors, may contribute to enhancing their malignant phenotypes. However, the effects of mtDNA abnormalities in colorectal cancer remain largely unknown. In this study, mtDNA-reduced cell model was established by partial depletion of mtDNA in SW480 cells and the effects of mtDNA reduction in colorectal cancer cells were investigated. We found that mtDNA-reduced cells had enhanced glucose uptake and generated markedly higher level of lactate...
April 20, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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