scholarly journals Hyperbaric Oxygen Therapy Represses the Warburg Effect and Epithelial–Mesenchymal Transition in Hypoxic NSCLC Cells via the HIF-1α/PFKP Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Linling Zhang ◽  
Jingjing Ke ◽  
Shengping Min ◽  
Nan Wu ◽  
Fei Liu ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Cell Lines ◽  
Hyperbaric Oxygen ◽  
Hyperbaric Oxygen Therapy ◽  
Warburg Effect ◽  
Oxygen Therapy ◽  
Nsclc Cell ◽  
Glycolytic Flux ◽  
Mesenchymal Transition ◽  
The Warburg Effect

BackgroundTumor cells initiate hypoxia-induced mechanisms to fuel cell proliferation, invasion, and metastasis, largely mediated by low O2-responsive Hypoxia-Inducible Factor 1 Alpha (HIF-1α). Therefore, hyperbaric oxygen therapy (HBO) is now being studied in cancer patients, but its impact upon non-small-cell lung cancer (NSCLC) cell metabolism remains uncharacterized.MethodsWe employed the NSCLC cell lines A549 and H1299 for in vitro studies. Glucose uptake, pyruvate, lactate, and adenosine triphosphate (ATP) assays were used to assess aerobic glycolysis (Warburg effect). A quantitative glycolytic flux model was used to analyze the flux contributions of HIF-1α-induced glucose metabolism genes. We used a Lewis lung carcinoma (LLC) murine model to measure lung tumorigenesis in C57BL/6J mice.ResultsHBO suppressed hypoxia-induced HIF-1α expression and downstream HIF-1α signaling in NSCLC cells. One HIF-1α-induced glucose metabolism gene—Phosphofructokinase, Platelet (PFKP)—most profoundly enhanced glycolytic flux under both low- and high-glucose conditions. HBO suppressed hypoxia-induced PFKP transactivation and gene expression via HIF-1α downregulation. HBO’s suppression of the Warburg effect, suppression of hyperproliferation, and suppression of epithelial-to-mesenchymal transition (EMT) in hypoxic NSCLC cell lines is mediated by the HIF-1α/PFKP axis. In vivo, HBO therapy inhibited murine LLC lung tumor growth in a Pfkp-dependent manner.ConclusionsHBO’s repression of the Warburg effect, repression of hyperproliferation, and repression of EMT in hypoxic NSCLC cells is dependent upon HIF-1α downregulation. HIF-1α’s target gene PFKP functions as a central mediator of HBO’s effects in hypoxic NSCLC cells and may represent a metabolic vulnerability in NSCLC tumors.

scholarly journals Targeting Glucose Metabolism of Cancer Cells with Dichloroacetate to Radiosensitize High-Grade Gliomas

2021 ◽  
Vol 22 (14) ◽  
pp. 7265
Author(s):  
Kristina M. Cook ◽  
Han Shen ◽  
Kelly J. McKelvey ◽  
Harriet E. Gee ◽  
Eric Hau
Keyword(s):  
Glucose Metabolism ◽  
Warburg Effect ◽  
High Grade Glioma ◽  
Glycolytic Flux ◽  
High Grade ◽  
Dna Breaks ◽  
Novel Approach ◽  
Altered Glucose ◽  
Altered Metabolism ◽  
The Warburg Effect

As the cornerstone of high-grade glioma (HGG) treatment, radiotherapy temporarily controls tumor cells via inducing oxidative stress and subsequent DNA breaks. However, almost all HGGs recur within months. Therefore, it is important to understand the underlying mechanisms of radioresistance, so that novel strategies can be developed to improve the effectiveness of radiotherapy. While currently poorly understood, radioresistance appears to be predominantly driven by altered metabolism and hypoxia. Glucose is a central macronutrient, and its metabolism is rewired in HGG cells, increasing glycolytic flux to produce energy and essential metabolic intermediates, known as the Warburg effect. This altered metabolism in HGG cells not only supports cell proliferation and invasiveness, but it also contributes significantly to radioresistance. Several metabolic drugs have been used as a novel approach to improve the radiosensitivity of HGGs, including dichloroacetate (DCA), a small molecule used to treat children with congenital mitochondrial disorders. DCA reverses the Warburg effect by inhibiting pyruvate dehydrogenase kinases, which subsequently activates mitochondrial oxidative phosphorylation at the expense of glycolysis. This effect is thought to block the growth advantage of HGGs and improve the radiosensitivity of HGG cells. This review highlights the main features of altered glucose metabolism in HGG cells as a contributor to radioresistance and describes the mechanism of action of DCA. Furthermore, we will summarize recent advances in DCA’s pre-clinical and clinical studies as a radiosensitizer and address how these scientific findings can be translated into clinical practice to improve the management of HGG patients.

scholarly journals Influence of SNF1 complex on growth, glucose metabolism and mitochondrial respiration ofSaccharomyces cerevisiae

2018 ◽  
Author(s):  
Cecilia Martinez-Ortiz ◽  
Andres Carrillo-Garmendia ◽  
Blanca Flor Correa-Romero ◽  
Melina Canizal-García ◽  
Juan Carlos González-Hernández ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Mitochondrial Respiration ◽  
Warburg Effect ◽  
Gene Deletion ◽  
Glycolytic Flux ◽  
Crabtree Effect ◽  
Main Pathway ◽  
Molecular Etiology ◽  
The Warburg Effect

AbstractThe switch of mitochondrial respiration to fermentation as the main pathway to produce ATP through the increase of glycolytic flux is known as the Crabtree effect. The elucidation of the molecular mechanism of the Crabtree effect may have important applications in ethanol production and lay the groundwork for the Warburg effect, which is essential in the molecular etiology of cancer. A key piece in this mechanism could be Snf1p, which is a protein that participates in the nutritional response that includes glucose metabolism. Thus, this work aimed to recognize the role of the SNF1 complex on the glycolytic flux and mitochondrial respiration, to gain insights about its relationship with the Crabtree effect. Herein, we found that inSaccharomyces cerevisiaecells grown at 1% glucose, mutation ofSNF1gene decreased glycolytic flux, increased NAD(P)H, enhancedHXK2gene transcription, and decreased mitochondrial respiration. Meanwhile, the same mutation increased the mitochondrial respiration of cells grown at 10% glucose. Moreover,SNF4gene deletion increased respiration and growth at 1% of glucose. In the case of theGAL83gene, we did not detect any change in mitochondrial respiration or growth. Altogether, these findings indicate thatSNF1is vital to switch from mitochondrial respiration to fermentation.

Experience in Applying Hyperbaric Oxygen Therapy Using Portable Pressure Chambers for the Treatment of Patients with the Novel Coronavirus Infection COVID-19

Biomeditsina ◽  
2020 ◽  
pp. 39-46
Author(s):  
A. S. Samoilov ◽  
Yu. D. Udalov ◽  
M. V. Sheyanov ◽  
A. V. Gholinsky ◽  
A. B. Litvinenko
Keyword(s):  
Oxygen Saturation ◽  
Hyperbaric Oxygen ◽  
Hyperbaric Oxygen Therapy ◽  
Oxygen Therapy ◽  
Capillary Blood ◽  
Blood Hemoglobin ◽  
Patient Groups ◽  
Radiological Changes ◽  
Coronavirus Infection ◽  
Novel Coronavirus

This communication presents the experience of using mobile pressure chambers in patients with the confi rmed novel coronavirus infection in hospital settings. The obtained preliminary results indicate positive antihypoxic effects of hyperbaric oxygen therapy (HBO) applied in the form of increased saturation. After a session of HBO, patients demonstrated an increase in the oxygen saturation of capillary blood hemoglobin at the average level of 3.71 points. Differences between SatO2 levels prior to and following HBO treatment were signifi cant in the CT2, CT3 and CT4 groups (p0.05). As expected, the effi cacy of HBO in terms of the oxygen saturation of capillary blood hemoglobin was the greatest in the patient groups showing pronounced clinical and radiological changes in the lungs.

Pengaruh Pemberian Terapi Oksigen Hiperbarik Terhadap Kadar Kolesterol Total Pada Tikus Putih (Rattus novergicus) Jantan Galur Wistar Yang Di Induksi Diet Tinggi Lemak

2018 ◽  
Vol 16 (1) ◽  
pp. 1 ◽  
Author(s):  
AZRUL HILDAN SAFRIZAL
Keyword(s):  
Cardiovascular Disease ◽  
Total Cholesterol ◽  
Cholesterol Level ◽  
Hyperbaric Oxygen ◽  
Hyperbaric Oxygen Therapy ◽  
High Fat Diet ◽  
Oxygen Therapy ◽  
Total Cholesterol Level ◽  
High Fat ◽  
Cholesterol Levels

<p>The pattern and lifestyle of today's society with the presence of an interner facility makes people spend more time sitting out than on exercise and increased consumption of high-fat foods may increase the risk of cardiovascular disease. An effective therapy is needed in preventing the occurrence of cardiovascular disease. Hyperbaric oxygen now starts to develop for the treatment of several diseases, which in turn can increase the gene forming antioxidant enzymes and ROS. To determine effect of hyperbaric oxygen therapy on total cholesterol levels of wistar white rats (Rattusnovergicus) induced bye high fat. The study was carried out in an expeative post test only group control of three groups. One group is given standard feed. All groups induced high-fat diet and standard feed. Of the two groups induced, one group was given hyperbaric oxygen therapy with a dose of 3 x 30 minutes for six days on day 7 at a blood test to determine total cholesterol levels<strong>. </strong>One way Anova parametric statistic test showed that p = 0.007 &lt; α proved hypothesis that hyperbaric oxygen therapy giving effect to total cholesterol level of white mice of jantangalurist rings induced by high fat diet. Total cholesterol was significantly different between K (-) and K (+) and between K (-) and P. It was found that hyperbaric oxygen therapy had an effect on total cholesterol level dose of 3x30 minutes for six days.</p>

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