Introduction to the molecular basis of cancer metabolism and the Warburg effect

Abstract

In differentiated normal cells, the conventional route of glucose metabolism involves glycolysis, followed by the citric acid cycle and electron transport chain to generate usable energy in the form of adenosine triphosphate (ATP). This occurs in the presence of oxygen. In hypoxic conditions, normal cells undergo anaerobic glycolysis to yield significantly less energy producing lactate as a product. As first highlighted in the 1920s by Otto Warburg, the metabolism exhibited by tumor cells involves an increased rate of aerobic glycolysis, known as the Warburg effect. In aerobic glycolysis, pyruvate molecules yielded from glycolysis are converted into fewer molecules of ATP even in the presence of oxygen. Evidence indicates that the reasons as to why tumor cells undergo aerobic glycolysis include: (1) the shift in priority to accumulate biomass rather than energy production, (2) the evasion of apoptosis as fewer reactive oxygen species are released by the mitochondria and (3) the production of lactate to further fuel growth of tumors. In this mini-review we discuss emerging molecular aspects of cancer metabolism and the Warburg effect. Aspects of the Warburg effect are analyzed in the context of the established hallmarks of cancer including the role of oncogenes and tumor suppressor genes.

Doxycycline inhibits proliferation and induces apoptosis of both human papillomavirus positive and negative cervical cancer cell lines

“…The majority of ATP production in mammalian cells are largely dependent on oxidative phosphorylation and glycolysis (Ngo et al 2015). As our studies and previous reports have shown that doxycycline affected both mitochondrial respiration and glycolysis (Fig.…”

Mutational load of the mitochondrial genome predicts pathological features and biochemical recurrence in prostate cancer

“…We predict 32% (24/74) of our identified mutations to have biological potential, with roughly half (9/24) present in sufficient frequency (>70%) to alter mitochondrial function. Further biological studies are required to determine the overall impact of these somatic mutations on energy metabolism, specifically their potential to drive tumor respiration from one of oxidative phosphorylation to aerobic glycolysis [29], a common cancer phenomenon known as the Warburg effect [30]. …”

Oxygen and viruses: a breathing story

“…This is known as the Warburg effect; it is less efficient in terms of ATP generation (2 vs 36 ATPs), but enables glucose to be used as a carbon source for the synthesis of nucleotides, amino acids and lipids for cell growth and division (Ngo et al, 2015). Some viruses can reprogramme cell metabolism to assist virus replication.…”