The cancer Warburg effect may be a testable example of the minimum entropy production rate principle

Abstract

Cancer cells consume more glucose by glycolytic fermentation to lactate than by respiration, a characteristic known as the Warburg effect. In contrast with the 36 moles of ATP produced by respiration, fermentation produces two moles of ATP per mole of glucose consumed, which poses a puzzle with regard to the function of the Warburg effect. The production of free energy (ΔG), enthalpy (ΔH), and entropy (ΔS) per mole linearly varies with the fraction (x) of glucose consumed by fermentation that is frequently estimated around 0.9. Hence, calculation shows that, in respect to pure respiration, the predominant fermentative metabolism decreases around 10% the production of entropy per mole of glucose consumed in cancer cells. We hypothesize that increased fermentation could allow cancer cells to accomplish the Prigogine theorem of the trend to minimize the rate of production of entropy. According to the theorem, open cellular systems near the steady state could evolve to minimize the rates of entropy production that may be reached by modified replicating cells producing entropy at a low rate. Remarkably, at CO concentrations above 930 ppm, glucose respiration produces less entropy than fermentation, which suggests experimental tests to validate the hypothesis of minimization of the rate of entropy production through the Warburg effect.

Phase transitions in tumor growth VI: Epithelial–Mesenchymal transition

“…where  represent the constant flux 11 k of the EMT, and the constants of Eq. (4. values, the systems display a hybrid epithelial-mesenchymal configuration, thus supporting previous reported experimental data suggesting that EMT is rarely an "allor-none" phenomenon [21] and exhibit a minimum entropy production rate [50]. Yet, a threshold value of 11 k can be recognized at which the transition from the epithelial to the mesenchymal phenotype emerge abruptly, like a "first order" phase transitions.…”

Obesity and Cancer Metastasis: Molecular and Translational Perspectives

“…An essential function of adipocytes is energy mobilization and therefore a metabolic interaction between cancer cells and adipocytes is not surprising. The Warburg effect suggests that due to mitochondrial dysfunction, malignant cells prefer to produce adenosine triphosphate (ATP) via glycolysis instead of oxidative phosphorylation, even in the presence of oxygen [129]. In parallel, cancer cells are able to use alternative sources of energy such as amino acids and lactate from the microenvironment.…”

The reverse Warburg effect is likely to be an Achilles' heel of cancer that can be exploited for cancer therapy

“…As one of the several hallmarks of cancer [ 1 ], the anomalous characteristic of energy metabolism pathway in cancer cells has received striking attention in the past decades [ 2 – 4 ], which is regarded as important as other features, such as sustained angiogenesis, avoiding immune destruction and so forth [ 5 ]. In the 1920s, the metabolic distinction between normal and tumor cells was firstly reported by Otto Warburg [ 6 ], termed as ‘the Warburg effect’, which suggests even in the presence of sufficient oxygen, the malignant cells prefer to produce adenosine triphosphate (ATP) via glycolysis Instead of oxidative phosphorylations (OXPHOs) [ 7 ]. The process is also called ‘aerobic glycolysis’.…”