ABSTRACT
Metabolic rearrangement is a typical hallmark of cancer cells ,especially the disorders in glucose metabolism. Normal cells rely on the steps of oxidative phosphorylation within the mitochondria to metabolize glucose and yield energy upon enough oxygen ,yet turning to glycolysis in the absence of oxygen . Nevertheless ,tumor cells exhibit high levels of glycolytic flux in different environments ,due to the requirement of malignant proliferation. This phenomenon was named as the Warburg effect ,the initiation of which is driven by multiple mechanisms ,including the influence of tumor microenvironment ,the activa?tion of tumor-promoting signaling pathways ,and the aberrant levels of metabolic enzymes. Moreover ,our recent findings sug?gest that inhibition of gluconeogenesis ,the general reversal of glycolysis ,would further promote the Warburg effect and tumor progression.
ABSTRACT
In this review, we bring further evidence in support of the hypothesis on the socalled respiratory and pH imbalance (RpHI) as a cause of long standing hypoxia within the whole organism, characteristic to the preneoplastic stage. Background: Carcinogenesis is a process by which normal cells are transformed into cancer cells. Cancer is a multifactorial disease with contributions from environmental, genetic and lifestyle factors. Cancer prevention is a global priority, yet the proximate causes of most cancers are still little understood. However, under hypoxic conditions, the overbusy cells, getting less oxygen than needed, turn into anaerobic adenosine triphosphate (ATP) production, excessive multiplication and finally, tumor development. Since hypoxia depends on the intensity and duration of action of the stress agent, human and animal organisms may compensate hypoxia only if the causal agent stops acting continuously. Cancer prevention might be associated with an increase in oxygen delivery to overstressed cells, carbon dioxide removing, as well as pH and glucose concentration balancing. The role of RpHI in chemical carcinogenesis and cancer incidence is also discussed. Conclusion: Evidence from the literature data is brought to show that cancers develop at the physiological level, while the molecular changes in cancer cells are the consequence and not the main cause of malign processes. A link between the Warburg effect and the Macovschi’s biostructural theory was suggested.