Teaching the basics of cancer metabolism: Developing antitumor strategies by exploiting the differences between normal and cancer cell metabolism

Abstract

This review of the basics of cancer metabolism focuses on exploiting the metabolic differences between normal and cancer cells. The first part of the review covers the different metabolic pathways utilized in normal cells to generate cellular energy, or ATP, and the glycolytic intermediates required to build the cellular machinery. The second part of the review discusses aerobic glycolysis, or the Warburg effect, and the metabolic reprogramming involving glycolysis, tricarboxylic acid cycle, and glutaminolysis in the context of developing targeted inhibitors in cancer cells. Finally, the selective targeting of cancer mitochondrial metabolism using positively charged lipophilic compounds as potential therapeutics and their ability to mitigate the toxic side effects of conventional chemotherapeutics in normal cells are discussed. I hope this graphical review will be useful in helping undergraduate, graduate, and medical students understand how investigating the basics of cancer cell metabolism could provide new insight in developing potentially new anticancer treatment strategies.

Effect of Mst1 on Endometriosis Apoptosis and Migration: Role of Drp1-Related Mitochondrial Fission and Parkin-Required Mitophagy

“…The supernatants were centrifuged at 10, 000 x g for 20 min at 4°C to acquire the pellets, which were spun again [6,24]. The final pellets were suspended in lysis buffer containing 1% Triton X-100 and were noted as mitochondrial-rich lysate fractions [34].…”

DUSP1 recuses diabetic nephropathy via repressing JNK‐Mff‐mitochondrial fission pathways

“…However, under conditions of hyperglycemia, the mitochondria become small, roundish fragments due to excessive fission, contributing to the progression of DN (Hu, Cheng, Xu, Ruf, & Lockwood, ; Zhou, Yue, Wang, Ma, & Chen, ). Previous findings indicate that hyperglycemia‐mediated mitochondrial fission evokes reactive oxygen species (ROS) overproduction, obligating cells to undergo oxidative stress (Kalyanaraman, ). In addition, uncontrolled mitochondrial division produces the most mitochondrial debris, leading to an inadequate distribution of mitochondrial DNA within the mitochondria (Brasacchio et al, ; Zhou et al, ).…”

Novel therapeutic roles of MC‐4 in combination with everolimus against advanced renal cell carcinoma by dual targeting of Akt/pyruvate kinase muscle isozyme M2 and mechanistic target of rapamycin complex 1 pathways

“…Similarly, we observed an increase in cellular lysosomes as well as autophagic vacuoles and empty autophagosomes, presumably with fully digested contents, following exposure to MC‐4+ everolimus in a morphological analysis by TEM (Figure H). In addition to its role in anabolic pathways, glutamine metabolism may also promote lactate accumulation and exacerbate glycolysis . Increased anabolic metabolite (lactate) and glutamine utilization via concomitant MC‐4+ everolimus‐induced Akt/PKM2 and mTORC1 pathways could have resulted in marked autophagic cell death (Figure I).…”

“…In addition to its role in anabolic pathways, glutamine metabolism may also promote lactate accumulation and exacerbate glycolysis. 24,25 Increased anabolic metabolite (lactate) and glutamine utilization via concomitant MC-4+ everolimus-induced Akt/PKM2 and mTORC1 pathways could have resulted in marked autophagic cell death ( Figure 3I). Therefore, mechanistically, we hypothesize that the modulation of autophagy and cancer cell metabolism by combination treatment with MC-4 and everolimus, the autophagy inducer, is a powerful approach that could markedly improve therapeutic outcomes in patients with advanced RCC.…”