Cancer and Glucose Metabolism: A Review on Warburg Mechanisms
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Abstract
Modification of all four major classes of macromolecules metabolism in cancer tissues is a common feature. This alteration is a requirement for rapid proliferation as it provides quick energy generation, enhanced macromolecule biosynthesis and maintenance of the redox state. In tumour cells, there is increased glucose metabolism to lactate in the presence of oxygen, a phenomenon known as the “Warburg effect”. Understanding the role of the Warburg effect in cancer progression and targeting this phenomenon as a possible target for cancer management has become paramount. Mechanisms such as acidification of tumour microenvironment, hypoxia-inducible factor (HIF) stabilisation, mutation of tumour suppressor genes and oncogenes, mitochondrial dysfunction, selected targeting by miRNA, altered glutamine metabolism and post-translational modifications have been found to induce the Warburg phenomenon. Other contributory mechanisms are isocitrate dehydrogenase gene mutation, mitochondria membrane transporters, and pyruvate dehydrogenase complex conditioning. Chemical compounds such as 2-deoxy-glucose, 3-bromopyruvate and dichloroacetic acid target this phenomenon to reverse altered metabolism. A better holistic understanding of these mechanisms will help uncover novel metabolism-based therapeutic strategies that may play a role in halting the Warburg effect and ultimately, cancer progression.
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