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Lactate AND mTOR

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https://www.readbyqxmd.com/read/27908730/mtor-activation-is-critical-for-betulin-treatment-in-renal-cell-carcinoma-cells
#1
Wenlong Cheng, Shiqi Ji, Haijian Zhang, Zhixing Han, Qingjun Liu, Jianwen Wang, Hao Ping
Betulin, a natural product isolated from the bark of the birch trees, exhibits multiple anticancer effects. Activation of mTOR signaling pathway has been found in numerous cancers, including renal cell carcinoma (RCC). Here, we attempted to study whether mTOR signaling was essential for betulin to treat RCC. Based on cell survival and colony formation assays, we found that mTOR hyperactive RCC cell line 786-O cells were more sensitive to betulin treatment compared with mTOR-inactive Caki-2 cells. Knockdown of TSC2 in Caki-2 cells had similar results to 786-O cells, and mTOR silencing in 786-O cells rescued the inhibitory effect of betulin, indicating that betulin inhibited RCC cell proliferation in an mTOR-dependent manner...
November 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27900044/plumbagin-inhibits-cell-proliferation-and-promotes-apoptosis-in-multiple-myeloma-cells-through-inhibition-of-the-pi3k-akt-mtor-pathway
#2
Hongwei Wu, Xiaozhen Dai, Enren Wang
Plumbagin is the primary component of the traditional Chinese medicine Baihua Dan, and possesses anti-infection and anticancer effects with the ability to enhance the sensitivity of tumor cells to radiation therapy. The present study aimed to investigate the potential anticancer effect and mechanism of plumbagin on multiple myeloma (MM) cells. Human MM OPM1 cells were treated with plumbagin, and its impact on cell viability, cytotoxicity, apoptosis and caspase-3 activity was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, lactate dehydrogenase leakage, flow cytometry and colorimetric assays...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27698900/anti-inflammatory-and-antitumor-activity-of-a-triple-therapy-for-a-colitis-related-colorectal-cancer
#3
Gabriela Figueroa-González, Verónica García-Castillo, Jossimar Coronel-Hernández, Eduardo López-Urrutia, Sonia León-Cabrera, Luis E Arias-Romero, L I Terrazas, Miriam Rodríguez-Sosa, Alma Delia Campos-Parra, Eduardo Zúñiga-Calzada, Cesar Lopez-Camarillo, Fermín Morales-González, Nadia J Jacobo-Herrera, Carlos Pérez-Plasencia
Colorectal cancer (CRC) is an important health issue worldwide, accounting for the third place of cancer incidence. Chronic inflammation, as seen in Crohn's disease and ulcerative colitis, is the most important risk factor for developing CRC, as it favours neoplastic transformation by enhancing epithelial cell turnover in the colonic mucosa. Treatments for CRC need to be improved; currently they are not specific and have several secondary effects in patients. The main objective of this work was to evaluate a new therapeutic strategy against a colitis-related colorectal cancer in vivo and in vitro by targeting mTOR-signaling and lactate dehydrogenase A...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27666003/basal-autophagy-protects-cardiomyocytes-from-doxorubicin-induced-toxicity
#4
Marcela Pizarro, Rodrigo Troncoso, Gonzalo J Martínez, Mario Chiong, Pablo F Castro, Sergio Lavandero
Doxorubicin (Doxo) is one of the most effective anti-neoplastic agents but its cardiotoxicity has been an important clinical limitation. The major mechanism of Doxo-induced cardiotoxicity is associated to its oxidative capacity. However, other processes are also involved with significant consequences for the cardiomyocyte. In recent years, a number of studies have investigated the role of autophagy on Doxo-induced cardiotoxicity but to date it is not clear how Doxo alters that process and its consequence on cardiomyocytes viability...
September 22, 2016: Toxicology
https://www.readbyqxmd.com/read/27602585/human-cytomegalovirus-encoded-chemokine-receptor-us28-activates-the-hif-1%C3%AE-pkm2-axis-in-glioblastoma-cells
#5
Raymond H de Wit, Azra Mujić-Delić, Jeffrey R van Senten, Alberto Fraile-Ramos, Marco Siderius, Martine J Smit
The human cytomegalovirus (HCMV) encoded chemokine receptor US28 promotes tumorigenesis through activation of various proliferative and angiogenic signaling pathways. Upon infection, US28 displays constitutive activity and signals in a G protein-dependent manner, hijacking the host's cellular machinery. In tumor cells, the hypoxia inducible factor-1α/pyruvate kinase M2 (HIF-1α/PKM2) axis plays an important role by supporting proliferation, angiogenesis and reprogramming of energy metabolism. In this study we show that US28 signaling results in activation of the HIF-1α/PKM2 feedforward loop in fibroblasts and glioblastoma cells...
September 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27498786/nitidine-chloride-inhibits-the-malignant-behavior-of-human-glioblastoma-cells-by-targeting-the-pi3k-akt-mtor-signaling-pathway
#6
Ming Liu, Jiwei Wang, Qichao Qi, Bin Huang, Anjing Chen, Xingang Li, Jian Wang
Recent studies have demonstrated that nitidine chloride (NC), a natural bioactive alkaloid, displays potent antitumor activity in various types of cancer. In the present study, NC was examined for efficacy in the treatment of human glioblastoma multiforme (GBM) as well as the molecular basis for its more general inhibitory effects in cancer. U251 and U87 GBM cell lines were exposed to three concentrations of NC (5, 25 and 50 µM) in vitro, and tumor cell growth was assessed on the basis of proliferation, migration and energy metabolism...
October 2016: Oncology Reports
https://www.readbyqxmd.com/read/27479743/metabolic-plasticity-underpins-innate-and-acquired-resistance-to-ldha-inhibition
#7
Aaron Boudreau, Hans E Purkey, Anna Hitz, Kirk Robarge, David Peterson, Sharada Labadie, Mandy Kwong, Rebecca Hong, Min Gao, Christopher Del Nagro, Raju Pusapati, Shuguang Ma, Laurent Salphati, Jodie Pang, Aihe Zhou, Tommy Lai, Yingjie Li, Zhongguo Chen, Binqing Wei, Ivana Yen, Steve Sideris, Mark McCleland, Ron Firestein, Laura Corson, Alex Vanderbilt, Simon Williams, Anneleen Daemen, Marcia Belvin, Charles Eigenbrot, Peter K Jackson, Shiva Malek, Georgia Hatzivassiliou, Deepak Sampath, Marie Evangelista, Thomas O'Brien
Metabolic reprogramming in tumors represents a potential therapeutic target. Herein we used shRNA depletion and a novel lactate dehydrogenase (LDHA) inhibitor, GNE-140, to probe the role of LDHA in tumor growth in vitro and in vivo. In MIA PaCa-2 human pancreatic cells, LDHA inhibition rapidly affected global metabolism, although cell death only occurred after 2 d of continuous LDHA inhibition. Pancreatic cell lines that utilize oxidative phosphorylation (OXPHOS) rather than glycolysis were inherently resistant to GNE-140, but could be resensitized to GNE-140 with the OXPHOS inhibitor phenformin...
October 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27387758/early-changes-in-the-metabolic-profile-of-activated-cd8-t-cells
#8
Clemens Cammann, Alexander Rath, Udo Reichl, Holger Lingel, Monika Brunner-Weinzierl, Luca Simeoni, Burkhart Schraven, Jonathan A Lindquist
BACKGROUND: Antigenic stimulation of the T cell receptor (TCR) initiates a change from a resting state into an activated one, which ultimately results in proliferation and the acquisition of effector functions. To accomplish this task, T cells require dramatic changes in metabolism. Therefore, we investigated changes of metabolic intermediates indicating for crucial metabolic pathways reflecting the status of T cells. Moreover we analyzed possible regulatory molecules required for the initiation of the metabolic changes...
2016: BMC Cell Biology
https://www.readbyqxmd.com/read/27384996/prognostic-significance-and-function-of-the-vacuolar-h-atpase-subunit-v1e1-in-esophageal-squamous-cell-carcinoma
#9
Sung Wook Son, Seok-Hyung Kim, Eun-Yi Moon, Dong-Hoon Kim, Suhkneung Pyo, Sung Hee Um
Vacuolar H+-ATPase (V-ATPase), a hetero-multimeric ATP-driven proton pump has recently emerged as a critical regulator of mTOR-induced amino acid sensing for cell growth. Although dysregulated activity of cell growth regulators is often associated with cancer, the prognostic significance and metabolic roles of V-ATPase in esophageal cancer progression remain unclear. Here, we show that high levels of V-ATPase subunit V1E1 (V-ATPase V1E1) were significantly associated with shortened disease-free survival in patients with esophageal squamous cell carcinoma (ESCC)...
June 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27236753/development-of-a-model-describing-regulation-of-casein-synthesis-by-the-mammalian-target-of-rapamycin-mtor-signaling-pathway-in-response-to-insulin-amino-acids-and-acetate
#10
J J Castro, S I Arriola Apelo, J A D R N Appuhamy, M D Hanigan
To improve dietary protein use efficiency in lactating cows, mammary protein synthesis responses to AA, energy substrates, and hormones must be better understood. These entities exert their effects through stimulation of mRNA translation via control of initiation and elongation rates at the cellular level. A central protein kinase of this phenomenon is the mammalian target of rapamycin (mTOR), which transfers the nutritional and hormonal stimuli onto a series of proteins downstream through a cascade of phosphorylation reactions that ultimately affect protein synthesis...
August 2016: Journal of Dairy Science
https://www.readbyqxmd.com/read/27210058/metformin-in-combination-with-5-fluorouracil-suppresses-tumor-growth-by-inhibiting-the-warburg-effect-in-human-oral-squamous-cell-carcinoma
#11
Koji Harada, Tarannum Ferdous, Toyoko Harada, Yoshiya Ueyama
Cancer cells show enhanced glucose consumption and lactate production even in the presence of abundant oxygen, a phenomenon known as the Warburg effect, which is related to tumor proliferation, progression and drug-resistance in cancers. Hypoxia-inducible factor-1 (HIF-1) and several members of Phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway positively contribute to the Warburg effect, whereas AMP activated protein Kinase (AMPK) acts as a negative regulator...
July 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27134166/metabolic-symbiosis-enables-adaptive-resistance-to-anti-angiogenic-therapy-that-is-dependent-on-mtor-signaling
#12
Elizabeth Allen, Pascal Miéville, Carmen M Warren, Sadegh Saghafinia, Leanne Li, Mei-Wen Peng, Douglas Hanahan
Therapeutic targeting of tumor angiogenesis with VEGF inhibitors results in demonstrable, but transitory efficacy in certain human tumors and mouse models of cancer, limited by unconventional forms of adaptive/evasive resistance. In one such mouse model, potent angiogenesis inhibitors elicit compartmental reorganization of cancer cells around remaining blood vessels. The glucose and lactate transporters GLUT1 and MCT4 are induced in distal hypoxic cells in a HIF1α-dependent fashion, indicative of glycolysis...
May 10, 2016: Cell Reports
https://www.readbyqxmd.com/read/27101297/concurrent-exercise-incorporating-high-intensity-interval-or-continuous-training-modulates-mtorc1-signaling-and-microrna-expression-in-human-skeletal-muscle
#13
Jackson J Fyfe, David J Bishop, Evelyn Zacharewicz, Aaron P Russell, Nigel K Stepto
We compared the effects of concurrent exercise, incorporating either high-intensity interval training (HIT) or moderate-intensity continuous training (MICT), on mechanistic target of rapamycin complex 1 (mTORC1) signaling and microRNA expression in skeletal muscle, relative to resistance exercise (RE) alone. Eight males (mean ± SD: age, 27 ± 4 yr; V̇o2 peak , 45.7 ± 9 ml·kg(-1)·min(-1)) performed three experimental trials in a randomized order: 1) RE (8 × 5 leg press repetitions at 80% 1-repetition maximum) performed alone and RE preceded by either 2) HIT cycling [10 × 2 min at 120% lactate threshold (LT); HIT + RE] or 3) work-matched MICT cycling (30 min at 80% LT; MICT + RE)...
June 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/27050525/err%C3%AE-regulated-lactate-metabolism-contributes-to-resistance-to-targeted-therapies-in-breast-cancer
#14
Sunghee Park, Ching-Yi Chang, Rachid Safi, Xiaojing Liu, Robert Baldi, Jeff S Jasper, Grace R Anderson, Tingyu Liu, Jeffrey C Rathmell, Mark W Dewhirst, Kris C Wood, Jason W Locasale, Donald P McDonnell
Imaging studies in animals and in humans have indicated that the oxygenation and nutritional status of solid tumors is dynamic. Furthermore, the extremely low level of glucose within tumors, while reflecting its rapid uptake and metabolism, also suggests that cancer cells must rely on other energy sources in some circumstances. Here, we find that some breast cancer cells can switch to utilizing lactate as a primary source of energy, allowing them to survive glucose deprivation for extended periods, and that this activity confers resistance to PI3K/mTOR inhibitors...
April 12, 2016: Cell Reports
https://www.readbyqxmd.com/read/27038740/angiotensin-iv-protects-cardiac-reperfusion-injury-by-inhibiting-apoptosis-and-inflammation-via-at4r-in-rats
#15
Byung Mun Park, Seung Ah Cha, Sun Hwa Lee, Suhn Hee Kim
Angiotensin IV (Ang IV) is formed by aminopeptidase N from Ang III by removing the first N-terminal amino acid. Previously, we reported that Ang III has some cardioprotective effects against global ischemia in Langendorff heart. However, it is not clear whether Ang IV has cardioprotective effects. The aim of the present study was to evaluate the effect of Ang IV on myocardial ischemia-reperfusion (I/R) injury in rats. Before ischemia, male Sprague-Dawley rats received Ang IV (1mg/kg/day) for 3 days. Anesthetized rats were subjected to 45min of ischemia by ligation of left anterior descending coronary artery followed by reperfusion and then, sacrificed 1 day or 1 week after reperfusion...
May 2016: Peptides
https://www.readbyqxmd.com/read/26997724/effect-of-pioglitazone-on-the-abrogated-cardioprotective-effect-of-ischemic-preconditioning-in-hyperlipidemic-rat-heart
#16
Dhiraj Mittal, Rajeev Taliyan, P L Sharma, Harlokesh Narayan Yadav
OBJECTIVES: The signaling pathways upstream of glycogen synthase kinase-3β (GSK-3β) get reduced during ischemic preconditioning (IPC) in hyperlipidemic rat heart. Pioglitazone, an insulin sensitizer, exerts cardioprotection through GSK-3β. The objective of the study is to investigate the role of pioglitazone on the attenuated cardioprotective effect of IPC in hyperlipidemic rat heart. MATERIALS AND METHODS: The rats were administered high-fat diet for 8 weeks to induce experimental hyperlipidemia (HL)...
January 2016: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/26993250/mitochondrial-function-and-glucose-metabolism-in-the-placenta-with-gestational-diabetes-mellitus-role-of-mir-143
#17
Sribalasubashini Muralimanoharan, Alina Maloyan, Leslie Myatt
A predisposing factor for development of the hyperglycaemic state of gestational diabetes mellitus (GDM) is obesity. We previously showed that increasing maternal obesity is associated with significant reductions in placental mitochondrial respiration. MicroRNA (miR)-143 has been previously shown to regulate the metabolic switch from oxidative phosphorylation to aerobic glycolysis in cancer tissues. We hypothesized that mitochondrial respiration is reduced and aerobic glycolysis is up-regulated via changes in miR-143 expression in the placenta of women with GDM...
June 1, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/26975021/metabolic-phenotype-of-bladder-cancer
#18
REVIEW
Francesco Massari, Chiara Ciccarese, Matteo Santoni, Roberto Iacovelli, Roberta Mazzucchelli, Francesco Piva, Marina Scarpelli, Rossana Berardi, Giampaolo Tortora, Antonio Lopez-Beltran, Liang Cheng, Rodolfo Montironi
Metabolism of bladder cancer represents a key issue for cancer research. Several metabolic altered pathways are involved in bladder tumorigenesis, representing therefore interesting targets for therapy. Tumor cells, including urothelial cancer cells, rely on a peculiar shift to aerobic glycolysis-dependent metabolism (the Warburg-effect) as the main energy source to sustain their uncontrolled growth and proliferation. Therefore, the high glycolytic flux depends on the overexpression of glycolysis-related genes (SRC-3, glucose transporter type 1 [GLUT1], GLUT3, lactic dehydrogenase A [LDHA], LDHB, hexokinase 1 [HK1], HK2, pyruvate kinase type M [PKM], and hypoxia-inducible factor 1-alpha [HIF-1α]), resulting in an overproduction of pyruvate, alanine and lactate...
April 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/26950449/isoflurane-preconditioning-protects-rat-brain-from-ischemia-reperfusion-injury-via-up-regulating-the-hif-1%C3%AE-expression-through-akt-mtor-s6k-activation
#19
W Yan, Z Chen, J Chen, H Chen
The volatile anesthetic isoflurane (ISO) has been widely used in ischemia reperfusion (IR) injury because its abilities to induce and trigger recovery are faster and smoother than other agents. However, the underlying molecular mechanisms for preconditioning the ISO in protecting the brain against IR injury are still largely unclear. In this paper, we investigated the neuroprotective effect of the ISO in the in vivo and in vitro models of IR injury and evaluated the possible correlation with Akt/mTOR/s6K signaling pathway...
2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/26935715/anti-proliferative-effect-of-rce-4-from-reineckia-carnea-on-human-cervical-cancer-hela-cells-by-inhibiting-the-pi3k-akt-mtor-signaling-pathway-and-nf-%C3%AE%C2%BAb-activation
#20
Caihong Bai, Xiaojiao Yang, Kun Zou, Haibo He, Junzhi Wang, Huilin Qin, Xiaoqin Yu, Chengxiong Liu, Juyan Zheng, Fan Cheng, Jianfeng Chen
Cervical cancer is the second leading cause of cancer deaths in women worldwide. In recent years, the studies find that inflammation is a critical component of tumor progression, and the ideal therapeutic methods should be aimed at the inflammation reaction triggers. (1β,3β,5β,25S)-spirostan-1,3-diol1-[α-L-rhamnopyranosyl-(1 → 2)-β-D-xylopyranoside] (RCE-4) was the main active composition of Reineckia carnea (Andr.) Kunth. It significantly induced apoptosis in cervical cancer Caski cells through the mitochondrial pathway in our previous studies; however, its underlying mechanism remains poorly understood...
June 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
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