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Warburg effect cancer

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https://www.readbyqxmd.com/read/28236852/the-promising-anticancer-drug-3-bromopyruvate-is-metabolized-through-glutathione-conjugation-which-affects-chemoresistance-and-clinical-practice-an-evidence-based-view
#1
Salah Mohamed El Sayed, Hussam Baghdadi, Mohammed Zolaly, Hamdi H Almaramhy, Mongi Ayat, Jagadish G Donki
3-Bromopyruvate (3BP) is a promising effective anticancer drug against many different tumors in children and adults. 3BP exhibited strong anticancer effects in both preclinical and human studies e.g. energy depletion, oxidative stress, anti-angiogenesis, anti-metastatic effects, targeting cancer stem cells and antagonizing the Warburg effect. There is no report about 3BP metabolism to guide researchers and oncologists to improve clinical practice and prevent drug resistance. In this article, we provide evidences that 3BP is metabolized through glutathione (GSH) conjugation as a novel report where 3BP was confirmed to be attached to GSH followed by permanent loss of pharmacological effects in a picture similar to cisplatin...
March 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28230866/oridonin-induces-autophagy-via-inhibition-of-glucose-metabolism-in-p53-mutated-colorectal-cancer-cells
#2
Zhuo Yao, Fuhua Xie, Min Li, Zirui Liang, Wenli Xu, Jianhua Yang, Chang Liu, Hongwangwang Li, Hui Zhou, Liang-Hu Qu
The Warburg effect is an important characteristic of tumor cells, making it an attractive therapeutic target. Current anticancer drug development strategies predominantly focus on inhibitors of the specific molecular effectors involved in tumor cell proliferation. These drugs or natural compounds, many of which target the Warburg effect and the underlying mechanisms, still need to be characterized. To elucidate the anticancer effects of a natural diterpenoid, oridonin, we first demonstrated the anticancer activity of oridonin both in vitro and in vivo in colorectal cancer (CRC) cells...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28218905/phosphorylation-mediated-activation-of-ldha-promotes-cancer-cell-invasion-and-tumour-metastasis
#3
L Jin, J Chun, C Pan, G N Alesi, D Li, K R Magliocca, Y Kang, Z G Chen, D M Shin, F R Khuri, J Fan, S Kang
Metastases remain the major cause of death from cancer. Recent molecular advances have highlighted the importance of metabolic alterations in cancer cells, including the Warburg effect that describes an increased glycolysis in cancer cells. However, how this altered metabolism contributes to tumour metastasis remains elusive. Here, we report that phosphorylation-induced activation of lactate dehydrogenase A (LDHA), an enzyme that catalyses the interconversion of pyruvate and lactate, promotes cancer cell invasion, anoikis resistance and tumour metastasis...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28216603/use-of-mature-mirna-strand-selection-in-mirnas-families-in-cervical-cancer-development
#4
REVIEW
Angelica Judith Granados-López, José Luis Ruiz-Carrillo, Luis Steven Servín-González, José Luis Martínez-Rodríguez, Claudia Araceli Reyes-Estrada, Rosalinda Gutiérrez-Hernández, Jesús Adrián López
Aberrant miRNA expression is well recognized as a cancer hallmark, nevertheless miRNA function and expression does not always correlate in patients tissues and cell lines studies. In addition to this issue, miRNA strand usage conduces to increased cell signaling pathways modulation diversifying cellular processes regulation. In cervical cancer, 20 miRNA families are involved in carcinogenesis induction and development to this moment. These families have 5p and 3p strands with different nucleotide (nt) chain sizes...
February 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28202516/modeling-the-genetic-regulation-of-cancer-metabolism-interplay-between-glycolysis-and-oxidative-phosphorylation
#5
Linglin Yu, Mingyang Lu, Dongya Jia, Jianpeng Ma, Eshel Ben-Jacob, Herbert Levine, Benny A Kaipparettu, Jose' N Onuchic
Abnormal metabolism is a hallmark of cancer, yet its regulation remains poorly understood. Cancer cells were considered to utilize primarily glycolysis for ATP production, referred to as the Warburg effect. However, recent evidence suggests that oxidative phosphorylation (OXPHOS) plays a crucial role during cancer progression. Here we utilized a systems biology approach to decipher the regulatory principle of glycolysis and OXPHOS. Integrating information from literature, we constructed a regulatory network of genes and metabolites from which we extracted a core circuit containing HIF-1, AMPK, and ROS...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197395/characterization-of-the-tumor-microenvironment-and-tumor-stroma-interaction-by-non-invasive-preclinical-imaging
#6
REVIEW
Nirilanto Ramamonjisoa, Ellen Ackerstaff
Tumors are often characterized by hypoxia, vascular abnormalities, low extracellular pH, increased interstitial fluid pressure, altered choline-phospholipid metabolism, and aerobic glycolysis (Warburg effect). The impact of these tumor characteristics has been investigated extensively in the context of tumor development, progression, and treatment response, resulting in a number of non-invasive imaging biomarkers. More recent evidence suggests that cancer cells undergo metabolic reprograming, beyond aerobic glycolysis, in the course of tumor development and progression...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28184935/involvement-of-ezh2-in-aerobic-glycolysis-of-prostate-cancer-through-mir-181b-hk2-axis
#7
Tao Tao, Ming Chen, Ranran Jiang, Han Guan, Yeqing Huang, Huan Su, Qiang Hu, Xu Han, Jun Xiao
Recent studies suggest that several types of tumors preferentially metabolize glucose through aerobic glycolysis, a phenomenon known as the Warburg effect. However, it remains largely unexplored whether metabolic reprogramming is involved in prostate cancer (PCa) progression. In this study, we found that histone methyltransferase enhancer of zeste homolog 2 (EZH2) dysregulated in PCa development regulated cellular growth and aerobic glycolysis through miR-181b/hexokinase 2 (HK2) axis. Aberrant expression profiles of coding RNA and microRNA were examined by two large, independent clinical prostate cancer data sets...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28183841/mathematical-modeling-links-wnt-signaling-to-emergent-patterns-of-metabolism-in-colon-cancer
#8
Mary Lee, George T Chen, Eric Puttock, Kehui Wang, Robert A Edwards, Marian L Waterman, John Lowengrub
Cell-intrinsic metabolic reprogramming is a hallmark of cancer that provides anabolic support to cell proliferation. How reprogramming influences tumor heterogeneity or drug sensitivities is not well understood. Here, we report a self-organizing spatial pattern of glycolysis in xenograft colon tumors where pyruvate dehydrogenase kinase (PDK1), a negative regulator of oxidative phosphorylation, is highly active in clusters of cells arranged in a spotted array. To understand this pattern, we developed a reaction-diffusion model that incorporates Wnt signaling, a pathway known to upregulate PDK1 and Warburg metabolism...
February 9, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28179591/correction-mtdna-depleted-pc3-cells-exhibit-warburg-effect-and-cancer-stem-cell-features
#9
Xiaoran Li, Yali Zhong, Jie Lu, Karol Axcrona, Lars Eide, Randi G Syljuåsen, Qian Peng, Junbai Wang, Hongquan Zhang, Mariusz Adam Goscinski, Gunnar Kvalheim, Jahn M Nesland, Zhenhe Suo
No abstract text is available yet for this article.
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28173837/insulin-like-growth-factor-1-receptor-activation-promotes-mammary-gland-tumor-development-by-increasing-glycolysis-and-promoting-biomass-production
#10
Bas Ter Braak, Christine L Siezen, Joo S Lee, Pooja Rao, Charlotte Voorhoeve, Eytan Ruppin, Jan Willem van der Laan, Bob van de Water
BACKGROUND: The insulin-like growth factor 1 (IGF1) signaling axis plays a major role in tumorigenesis. In a previous experiment, we chronically treated mice with several agonists of the IGF1 receptor (IGF1R). We found that chronic treatment with insulin analogues with high affinity towards the IGF1R (IGF1 and X10) decreased the mammary gland tumor latency time in a p53(R270H/+)WAPCre mouse model. Frequent injections with insulin analogues that only mildly activated the IGF1R in vivo (glargine and insulin) did not significantly decrease the tumor latency time in this mouse model...
February 7, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28168164/vdac-tubulin-an-anti-warburg-pro-oxidant-switch
#11
REVIEW
Eduardo N Maldonado
Aerobic enhanced glycolysis characterizes the Warburg phenotype. In cancer cells, suppression of mitochondrial metabolism contributes to maintain a low ATP/ADP ratio that favors glycolysis. We propose that the voltage-dependent anion channel (VDAC) located in the mitochondrial outer membrane is a metabolic link between glycolysis and oxidative phosphorylation in the Warburg phenotype. Most metabolites including respiratory substrates, ADP, and Pi enter mitochondria only through VDAC. Oxidation of respiratory substrates in the Krebs cycle generates NADH that enters the electron transport chain (ETC) to generate a proton motive force utilized to generate ATP and to maintain mitochondrial membrane potential (ΔΨ)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28167100/cancer-metabolism-in-space-and-time-beyond-the-warburg-effect
#12
Pierre Danhier, Piotr Bański, Valéry L Payen, Debora Grasso, Luigi Ippolito, Pierre Sonveaux, Paolo E Porporato
Altered metabolism in cancer cells is pivotal for tumor growth, most notably by providing energy, reducing equivalents and building blocks while several metabolites exert a signaling function promoting tumor growth and progression. A cancer tissue cannot be simply reduced to a bulk of proliferating cells. Tumors are indeed complex and dynamic structures where single cells can heterogeneously perform various biological activities with different metabolic requirements. Because tumors are composed of different types of cells with metabolic activities affected by different spatial and temporal contexts, it is important to address metabolism taking into account cellular and biological heterogeneity...
February 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28143530/a-first-immunohistochemistry-study-of-transketolase-and-transketolase-like-1-expression-in-canine-hyperplastic-and-neoplastic-mammary-lesions
#13
Giovanni Pietro Burrai, Alessandro Tanca, Tiziana Cubeddu, Marcello Abbondio, Marta Polinas, Maria Filippa Addis, Elisabetta Antuofermo
BACKGROUND: Canine mammary tumors represent the most common neoplasm in female dogs, and the discovery of cancer biomarkers and their translation to clinical relevant assays is a key requirement in the war on cancer. Since the description of the 'Warburg effect', the reprogramming of metabolic pathways is considered a hallmark of pathological changes in cancer cells. In this study, we investigate the expression of two cancer-related metabolic enzymes, transketolase (TKT) and transketolase-like 1 (TKTL1), involved in the pentose phosphate pathway (PPP), an alternative metabolic pathway for glucose breakdown that could promote cancer by providing the precursors and energy required for rapidly growing cells...
January 31, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28122260/out-of-warburg-effect-an-effective-cancer-treatment-targeting-the-tumor-specific-metabolism-and-dysregulated-ph
#14
REVIEW
Laurent Schwartz, Thomas Seyfried, Khalid O Alfarouk, Jorgelindo Da Veiga Moreira, Stefano Fais
As stated by Otto Warburg nearly a century ago, cancer is a metabolic disease, a fermentation caused by malfunctioning mitochondria, resulting in increased anabolism and decreased catabolism. Treatment should, therefore, aim at restoring the energy yield. To decrease anabolism, glucose uptake should be reduced (ketogenic diet). To increase catabolism, the oxidative phosphorylation should be restored. Treatment with a combination of α-lipoic acid and hydroxycitrate has been shown to be effective in multiple animal models...
January 22, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28122247/arginine-deprivation-inhibits-the-warburg-effect-and-upregulates-glutamine-anaplerosis-and-serine-biosynthesis-in-ass1-deficient-cancers
#15
Jeff Charles Kremer, Bethany Cheree Prudner, Sara Elaine Stubbs Lange, Gregory Richard Bean, Matthew Bailey Schultze, Caitlyn Brook Brashears, Megan DeAnna Radyk, Nathan Redlich, Shin-Cheng Tzeng, Kenjiro Kami, Laura Shelton, Aixiao Li, Zack Morgan, John Stephen Bomalaski, Takashi Tsukamoto, Jon McConathy, Loren Scott Michel, Jason Matthew Held, Brian Andrew Van Tine
Targeting defects in metabolism is an underutilized strategy for the treatment of cancer. Arginine auxotrophy resulting from the silencing of argininosuccinate synthetase 1 (ASS1) is a common metabolic alteration reported in a broad range of aggressive cancers. To assess the metabolic effects that arise from acute and chronic arginine starvation in ASS1-deficient cell lines, we performed metabolite profiling. We found that pharmacologically induced arginine depletion causes increased serine biosynthesis, glutamine anaplerosis, oxidative phosphorylation, and decreased aerobic glycolysis, effectively inhibiting the Warburg effect...
January 24, 2017: Cell Reports
https://www.readbyqxmd.com/read/28120890/systems-biology-analysis-of-drivers-underlying-hallmarks-of-cancer-cell-metabolism
#16
Daniel C Zielinski, Neema Jamshidi, Austin J Corbett, Aarash Bordbar, Alex Thomas, Bernhard O Palsson
Malignant transformation is often accompanied by significant metabolic changes. To identify drivers underlying these changes, we calculated metabolic flux states for the NCI60 cell line collection and correlated the variance between metabolic states of these lines with their other properties. The analysis revealed a remarkably consistent structure underlying high flux metabolism. The three primary uptake pathways, glucose, glutamine and serine, are each characterized by three features: (1) metabolite uptake sufficient for the stoichiometric requirement to sustain observed growth, (2) overflow metabolism, which scales with excess nutrient uptake over the basal growth requirement, and (3) redox production, which also scales with nutrient uptake but greatly exceeds the requirement for growth...
January 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28106737/a-novel-combination-rnai-toward-warburg-effect-by-replacement-with-mir-145-and-silencing-of-ptbp1-induces-apoptotic-cell-death-in-bladder-cancer-cells
#17
Tomoaki Takai, Yuki Yoshikawa, Teruo Inamoto, Koichiro Minami, Kohei Taniguchi, Nobuhiko Sugito, Yuki Kuranaga, Haruka Shinohara, Minami Kumazaki, Takuya Tsujino, Kiyoshi Takahara, Yuko Ito, Yukihiro Akao, Haruhito Azuma
Bladder cancer is one of the most difficult malignancies to control. We explored the use of a novel RNA-interference method for a driver oncogene regulating cancer specific energy metabolism by the combination treatment with a small interfering RNA (siRNA) and a microRNA. After transfection of T24 and 253JB-V cells with miR-145 and/or siR-PTBP1, we examined the effects of cell growth and gene expression by performing the trypan blue dye exclusion test, Western blot, Hoechst 33342 staining, reverse transcription polymerase chain reaction (RT-PCR), and electron microscopy...
January 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28105937/effect-of-lentivirus-mediated-shrna-inactivation-of-hk1-hk2-and-hk3-genes-in-colorectal-cancer-and-melanoma-cells
#18
Anna V Kudryavtseva, Maria S Fedorova, Alex Zhavoronkov, Alexey A Moskalev, Alexander S Zasedatelev, Alexey A Dmitriev, Asiya F Sadritdinova, Irina Y Karpova, Kirill M Nyushko, Dmitry V Kalinin, Nadezhda N Volchenko, Nataliya V Melnikova, Kseniya M Klimina, Dmitry V Sidorov, Anatoly Y Popov, Tatiana V Nasedkina, Andrey D Kaprin, Boris Y Alekseev, George S Krasnov, Anastasiya V Snezhkina
BACKGROUND: The switch from oxidative phosphorylation to glycolysis in proliferating cancer cells, even under aerobic conditions, has been shown first in 1926 by Otto Warburg. Today this phenomenon is known as the "Warburg effect" and recognized as a hallmark of cancer. The metabolic shift to glycolysis is associated with the alterations in signaling pathways involved in energy metabolism, including glucose uptake and fermentation, and regulation of mitochondrial functions. Hexokinases (HKs), which catalyze the first step of glycolysis, have been identified to play a role in tumorigenesis of human colorectal cancer (CRC) and melanoma...
December 22, 2016: BMC Genetics
https://www.readbyqxmd.com/read/28098871/lectin-pcl-inhibits-the-warburg-effect-of-pc3-cells-by-combining-with-egfr-and-inhibiting-hk2
#19
Hong Zhang, Xia Du, Ting-Ting Sun, Chun-Liu Wang, Ye Li, Shou-Zhen Wu
Prostatic carcinoma is the most aggressive tumor in adult men. Warburg effect is an important characteristic of tumor cell metabolism including prostate cancer cells, in which hexokinase 2 (HK2), a major rate-limiting enzyme involved in Warburg effect, is selectively upregulated. The lectin PCL is a mannose binding lectin which induces tumor cell apoptosis and autophagy. In the present study, we report that PCL could lower glucose consumption and lactate production, shift the Warburg effect by inhibiting the expression of HK2 in PC3 cells and the suppression of HK2 by siRNA reversed the effect of PCL on glucose consumption and lactate production...
January 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28094552/glucose-metabolism-in-cancer-and-ischemia-possible-therapeutic-consequences-of-the-warburg-effect
#20
Spela Salamon, Eva Podbregar, Peter Kubatka, Dietrich Büsselberg, Martin Caprnda, Radka Opatrilova, Vanda Valentova, Mariusz Adamek, Peter Kruzliak, Matej Podbregar
The Warburg effect states that the main source of energy for cancer cells is not aerobic respiration, but glycolysis-even in normoxia. The shift from one to the other is governed by mutually counteracting enzymes: pyruvate dehydrogenase and pyruvate dehydrogenase kinase (PDK). Anaerobic metabolism of cancer cells promotes cell proliferation, local tissue immunosuppression, resistance to hypoxic conditions, and metastatic processes. By switching glucose back to oxidative metabolism, these effects might be reversed...
February 2017: Nutrition and Cancer
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