The Warburg Effect 97 Years after Its Discovery

Pascale, Rosa M.; Calvisi, Diego F.; Simile, Maria M.; Feo, Claudio F; Feo, Francesco

doi:10.3390/cancers12102819

Cited by 175 publications

(137 citation statements)

References 250 publications

(300 reference statements)

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“…The glucometabolic reprogramming that occurs in many cancer cells, and in other diseased cells as well [ 1 , 2 ], shifts ATP production away from the mitochondria and into the cytosol; this can occur even when ample oxygen is available and is referred to as aerobic glycolysis or the Warburg effect [ 3 , 4 ]. This change permits cancer cells to rapidly proliferate since it is accompanied by the upregulation of the pentose phosphate pathway (also known as the phosphogluconate pathway or the hexose monophosphate shunt) which provides abundant amounts of ribose-5-phosphate, a necessary constituent that supports nucleotide production [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases

Reíter

Sharma

Rosales-Corral

2021

IJMS

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Glucose is an essential nutrient for every cell but its metabolic fate depends on cellular phenotype. Normally, the product of cytosolic glycolysis, pyruvate, is transported into mitochondria and irreversibly converted to acetyl coenzyme A by pyruvate dehydrogenase complex (PDC). In some pathological cells, however, pyruvate transport into the mitochondria is blocked due to the inhibition of PDC by pyruvate dehydrogenase kinase. This altered metabolism is referred to as aerobic glycolysis (Warburg effect) and is common in solid tumors and in other pathological cells. Switching from mitochondrial oxidative phosphorylation to aerobic glycolysis provides diseased cells with advantages because of the rapid production of ATP and the activation of pentose phosphate pathway (PPP) which provides nucleotides required for elevated cellular metabolism. Molecules, called glycolytics, inhibit aerobic glycolysis and convert cells to a healthier phenotype. Glycolytics often function by inhibiting hypoxia-inducible factor-1α leading to PDC disinhibition allowing for intramitochondrial conversion of pyruvate into acetyl coenzyme A. Melatonin is a glycolytic which converts diseased cells to the healthier phenotype. Herein we propose that melatonin’s function as a glycolytic explains its actions in inhibiting a variety of diseases. Thus, the common denominator is melatonin’s action in switching the metabolic phenotype of cells.

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Section: Introductionmentioning

confidence: 99%

Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases

Reíter

Sharma

Rosales-Corral

2021

IJMS

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“…According to the original version of the “Warburg hypothesis”, cancer cells switch to glycolysis from oxidative phosphorylation. However, more recent data indicate that many cancer cells, while upregulating glycolysis (as well as glutaminolysis, and many additional metabolic pathways) can also maintain or even increase their aerobic ATP generation via the stimulation of mitochondrial electron transport [ 101 , 102 , 103 , 104 , 105 , 106 ]. To anthropomorphize: maximizing ATP generation is the cancer cell’s primary “metabolic goal”: whatever biochemical mechanism serves this goal—even if it is ”wasteful” or perhaps useful in the short-term but detrimental in the longer-term—will be deemed ‘good enough’ to satisfy the “short-term thinking” of the cancer cell.…”

Section: Upregulation Of Various H 2 S-producinmentioning

confidence: 99%

Hydrogen Sulfide, an Endogenous Stimulator of Mitochondrial Function in Cancer Cells

Szabó

2021

Cells

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Hydrogen sulfide (H2S) has a long history as toxic gas and environmental hazard; inhibition of cytochrome c oxidase (mitochondrial Complex IV) is viewed as a primary mode of its cytotoxic action. However, studies conducted over the last two decades unveiled multiple biological regulatory roles of H2S as an endogenously produced mammalian gaseous transmitter. Cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST) are currently viewed as the principal mammalian H2S-generating enzymes. In contrast to its inhibitory (toxicological) mitochondrial effects, at lower (physiological) concentrations, H2S serves as a stimulator of electron transport in mammalian mitochondria, by acting as an electron donor—with sulfide:quinone oxidoreductase (SQR) being the immediate electron acceptor. The mitochondrial roles of H2S are significant in various cancer cells, many of which exhibit high expression and partial mitochondrial localization of various H2S producing enzymes. In addition to the stimulation of mitochondrial ATP production, the roles of endogenous H2S in cancer cells include the maintenance of mitochondrial organization (protection against mitochondrial fission) and the maintenance of mitochondrial DNA repair (via the stimulation of the assembly of mitochondrial DNA repair complexes). The current article overviews the state-of-the-art knowledge regarding the mitochondrial functions of endogenously produced H2S in cancer cells.

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“…This switch from oxidative phosphorylation to glycolysis allows cancer cells to meet the anabolic demands that result from their dysregulated cellular growth and altered differentiation. Ultimately, cancer cells develop a unique metabolic profile that distinguishes them from normal cells [ 42 , 43 , 44 , 45 ]. If this idea is pursued a bit further, one may hypothesize that different tumors arising in different tissue types may each have a cancer metabolite profile that is distinct from that of another tumor type.…”

Section: Metabolomics As a Potential New Way To Diagnose And Classmentioning

confidence: 99%

The Distinctive Serum Metabolomes of Gastric, Esophageal and Colorectal Cancers

Ren

Rajani

Wang

2021

Cancers

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Three of the most lethal cancers in the world are the gastrointestinal cancers—gastric (GC), esophageal (EC) and colorectal cancer (CRC)—which are ranked as third, sixth and fourth in cancer deaths globally. Early detection of these cancers is difficult, and a quest is currently on to find non-invasive screening tests to detect these cancers. The reprogramming of energy metabolism is a hallmark of cancer, notably, an increased dependence on aerobic glycolysis which is often referred to as the Warburg effect. This metabolic change results in a unique metabolic profile that distinguishes cancer cells from normal cells. Serum metabolomics analyses allow one to measure the end products of both host and microbiota metabolism present at the time of sample collection. It is a non-invasive procedure requiring only blood collection which encourages greater patient compliance to have more frequent screenings for cancer. In the following review we will examine some of the most current serum metabolomics studies in order to compare their results and test a hypothesis that different tumors, notably, from EC, GC and CRC, have distinguishing serum metabolite profiles.

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The Warburg Effect 97 Years after Its Discovery

Cited by 175 publications

References 250 publications

Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases

Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases

Hydrogen Sulfide, an Endogenous Stimulator of Mitochondrial Function in Cancer Cells

The Distinctive Serum Metabolomes of Gastric, Esophageal and Colorectal Cancers

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