scholarly journals Anticancer strategies based on the metabolic profile of tumor cells: therapeutic targeting of the Warburg effect

2016 ◽  
Vol 37 (8) ◽  
pp. 1013-1019 ◽  
Author(s):  
Xi-sha Chen ◽  
Lan-ya Li ◽  
Yi-di Guan ◽  
Jin-ming Yang ◽  
Yan Cheng
2015 ◽  
Vol 75 (16) ◽  
pp. 3355-3364 ◽  
Author(s):  
N.V. Rajeshkumar ◽  
Prasanta Dutta ◽  
Shinichi Yabuuchi ◽  
Roeland F. de Wilde ◽  
Gary V. Martinez ◽  
...  

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1177
Author(s):  
Johannes H.G.M. van Beek

Background: Tumor cells show the Warburg effect: high glucose uptake and lactate production despite sufficient oxygen supply. Otto Warburg found this effect in tissue slices and in suspensions of Ehrlich ascites tumor cells. Remarkably, these ascites tumor cells can transiently take up glucose an order of magnitude faster than the steady high rate measured by Warburg for hours. Methods: The purpose of the transiently very high glucose uptake is investigated here with a computational model of glycolysis, oxidative phosphorylation and ATP consumption which reproduces short kinetic experiments on the ascites tumor cells as well as the long-lasting Warburg, Crabtree and Pasteur effects. The model, extended with equations for glucose and O2 transport in tissue, is subsequently used to predict metabolism in tumor cells during fluctuations of tissue blood flow resulting in cycling hypoxia. Results: The model analysis suggests that the head section of the glycolytic chain in the tumor cells is partially inhibited in about a minute when substantial amounts of glucose have been taken up intracellularly; this head section of the glycolytic chain is subsequently disinhibited slowly when concentrations of glycolytic intermediates are low. Based on these dynamic characteristics, simulations of tissue with fluctuating O2 and glucose supply predict that tumor cells greedily take up glucose when this periodically becomes available, leaving very little for other cells. The glucose is stored as fructose 1,6-bisphosphate and other glycolytic intermediates, which are used for ATP production during   O2 and glucose shortages. Conclusions: The head section of glycolysis which phosphorylates glucose may be dynamically regulated and takes up glucose at rates exceeding the Warburg effect if glucose levels have been low for some time. The hypothesis is put forward here that dynamic regulation of the powerful glycolytic enzyme system in tumors is used to buffer oxygen and nutrient fluctuations in tissue.


Author(s):  
Li Li ◽  
Yan Ma ◽  
Kamalibaike Maerkeya ◽  
Davuti Reyanguly ◽  
Lili Han

Hypoxia reprogrammed glucose metabolism affects the Warburg effect of tumor cells, but the mechanism is still unclear. Long-chain non-coding RNA (lncRNA) has been found by many studies to be involved in the Warburg effect of tumor cells under hypoxic condition. Herein, we find that lncRNA OIP5-AS1 is up-regulated in cervical cancer tissues and predicts poor 5-years overall survival in cervical cancer patients, and it promotes cell proliferation of cervical cancer cells in vitro and in vivo. Moreover, OIP5-AS1 is a hypoxia-responsive lncRNA and is essential for hypoxia-enhanced glycolysis which is IDH2 or hypoxia inducible factor-1α (HIF-1α) dependent. In cervical cancer cells, OIP5-AS1 promotes IDH2 expression by inhibiting miR-124-5p, and IDH2 promotes the Warburg effect of cervical under hypoxic condition through regulating HIF-1α expression. In conclusion, hypoxia induced OIP5-AS1 promotes the Warburg effect through miR-124-5p/IDH2/HIF-1α pathway in cervical cancer.


2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Roberto Flores ◽  
Laura Shelton ◽  
Ashley Brown ◽  
Luke Taus ◽  
Frank Glover ◽  
...  

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1177
Author(s):  
Johannes H.G.M. van Beek

Background: Tumor cells often show altered metabolism which supports uncontrolled proliferation. A classic example is the Warburg effect: high glucose uptake and lactate production despite sufficient oxygen supply. Remarkably, tumor cells can transiently take up glucose even an order of magnitude faster when glucose is reintroduced after depletion. Regulation and significance of this high glucose uptake are investigated here. Methods: A new computational model was developed which reproduces two types of experimental data on Ehrlich ascites tumor cells: measurements by Otto Warburg of the average aerobic glycolytic rate during one hour (Warburg effect), and fast metabolic responses measured by others during the first minutes after reintroducing glucose. The model is subsequently extended with equations for glucose and O2 transport to predict the role of metabolism during fluctuations of blood flow in tumor tissue. Results: Model analysis reveals dynamic regulation of the head section of glycolysis where glucose uptake and phosphorylation occur. The head section is disinhibited slowly when concentrations of glycolytic intermediates fall, causing glucose uptake rate to considerably exceed that found by Warburg. The head section is partially inhibited in about a minute when sufficient glucose has been taken up. Simulations predict that tumors greedily take up glucose when blood flow resumes after periods of low flow. The cells then store glucose as fructose 1,6-bisphosphate and other glycolytic intermediates. During subsequent periods of low flow that cause O2 and glucose depletion these stores are used for ATP production and biomass. Conclusions: The powerful glycolytic system in tumors not only synthesizes ATP at high steady rates, but can also store glycolytic intermediates to buffer temporary oxygen and nutrient shortages for up to 10 minutes. The head section of glycolysis in tumor cells, disinhibited during glucose shortages, becomes very efficient at stealing glucose from other cells, even at low glucose concentrations.


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