Pieces of the Complex Puzzle of Cancer Cell Energy Metabolism: An Overview of Energy Metabolism and Alternatives for Targeted Cancer Therapy

Abstract

Over the past decades, several advances in cancer cell biology have led to relevant details about a phenomenon called "Warburg effect". Currently, it has been accepted that Warburg effect is not anymore compatible with all cancer cells, and thus the process of aerobic glycolysis is now challenged by the knowledge of a large number of cells presenting mitochondrial function. The energy metabolism of cancer cells is focused in the bioenergetic and biosynthetic pathways to meet the requirements of rapid proliferation. Changes in the metabolism of carbohydrate, amino acids and lipids have already been reported in cancer cells and might play relevant roles for cancer progression. To the best of our knowledge, mostly of these changes are established, mainly due to genetic reprogramming that leads to the transformation of a healthy into a cancerous cell. Indeed, several enzymes of high relevance for the energy are targets of oncogenes (ex. PI3K, HIF1 and Myc) and tumor suppressor proteins (ex. p53). As a consequence of the extensive study on cancer cell metabolism, some new therapeutic strategies have appeared that aim to interrupt the aberrant metabolism, as well as the influence of genetic reprogramming in cancer cells. In this perspective, we briefly review the cancer cell metabolism (carbohydrate, amino acid and lipid), and also describe oncogenes and tumor suppressors that affect cancer cell metabolism. We also discuss some potential candidates for target therapy to disrupt the main driven-force for cancer cell metabolism and proliferation.

Role of a lipid metabolism-related lncRNA signature in risk stratification and immune microenvironment for colon cancer

“…We confirmed that lipid metabolism-related lncRNAs may serve as a signature for predicting survival Energy metabolism reprogramming is an important feature of tumors [21,22]. The imbalance among oncogenic pathways interferes with the synthesis and metabolism of various substances, including glucose, glutamine, and fatty acids, thereby promoting the growth of tumor cells [23][24][25]. To date, studies on the association of lncRNA expression with lipid metabolism in colon cancer are scarcely reported.…”

Understanding the Mechanism of Action of Melatonin, Which Induces ROS Production in Cancer Cells

“…Therefore, it is also suggested that the underlying mechanism of the pro-oxidant effect of melatonin on cancer cells involves the inhibition of HIF-1α by melatonin. HIF-1α is a key transcription agent involved in mediating Warburg-type metabolisms in diseased cells [ 62 , 63 ]. HIF-1α is also part of an oxygen sensing system that is activated when the partial pressure (pO 2 ) of intracellular oxygen becomes depressed.…”

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

“…Within a given solid tumor there may be a gradient from near the center of the tumor where the oxygen tension is lowest to the periphery where the cells may be normoxic; this is also reflected in the intensity of HIF-1α expression [ 104 , 105 , 106 , 107 ]. Unequivocally, HIF-1α has a central role in orchestrating the processes that allow cancer cells (and other diseased cells) to accommodate aerobic glycolysis [ 108 , 109 ]. Under normoxic conditions, in which most cells exist, HIF-1α subunits are ubiquitinated by the von Hippel–Landau complex and quickly undergo proteasomal degradation, so it has little effect on glucose metabolism or oxidation [ 110 , 111 ].…”