Current Pharmaceutical Biotechnology - Volume 14, Issue 3, 2013

High glucose uptake is a characteristic of most metastatic tumors and activation of Ras signaling in immortalized cells increases glycolytic flux into lactate, de novo nucleic acid synthesis and the tricarboxylic acid cycle, and increases NADH shuttling, oxygen consumption and uncoupling of ATP synthase from the proton gradient. Fructose-2,6- bisphosphate, C-Myc, HIF1α and AKT each have been found to be key regulators of gly Read More

Accumulated evidence suggests that p53 plays an important role in the regulation of metabolism and intracellular redox homeostasis through transcription-dependent and -independent mechanisms. Mitochondria, the power plant of cells, provide cells with ATP for their functions by regulating energy metabolism. In addition, as the byproducts of metabolism, reactive oxygen species (ROS) generated in the mitochond Read More

Experimental and epidemiological evidence supports the idea that dietary fat and fiber influence colon carcinogenesis. Particularly, their components, n-3 polyunsaturated fatty acids (PUFAs) and butyrate, have been proven to exhibit beneficial effects on colon epithelial cell metabolism, signaling, and kinetics, thus preventing colon inflammation and cancer. Moreover, these effects may be strengthened by P Read More

The proliferative cancer cell paradigm that has driven cancer drug development for the past 50 years has failed to generate treatments that cure most metastatic adult cancers. This view is supported not only by cumulative experience with conventional cytotoxic anticancer drugs, but also by the application of highly-targeted anticancer compounds against, for example, BCR-ABL in CML and mutant BRAF in metastatic melano Read More

Positron emission tomography (PET) is a molecular imaging modality that provides the opportunity to rapidly and non-invasively visualize tumors derived from multiple organs. In order to do so, PET utilizes radiotracers, such as 18F-FDG and 11C-acetate, whose uptake coincides with altered metabolic pathways within tumors. Increased expression and activity of enzymes in the fatty acid synthesis pathway is a frequent hallm Read More

Oncogene-driven proliferative signaling in tumor cells requires comprehensive upregulation of cellular energy metabolism and macromolecule syntheses. These alterations are now known to include not only upregulated glycolysis, but also increased fatty acid metabolism, glutaminolysis, deregulated mitochondrial function and more. Many prospective targets for tumor-specific pharmacological modulation of metabolism h Read More

Mitochondria are known to play a key role in various cellular processes essential to both the life and death of cells, including calcium homeostasis, programmed cell death, and energy metabolism. Over 80 years ago, Otto Warburg discovered that in contrast to normal cells which produce most of their ATP via mitochondrial oxidative phosphorylation, cancer cells preferentially utilize glycolysis for production of ATP, a phenomeno Read More

Tumor cells show metabolic features distinctive from normal tissues, with characteristically enhanced aerobic glycolysis, glutaminolysis and lipid synthesis. Peroxisome proliferator activated receptor α (PPAR α) is activated by nutrients (fatty acids and their derivatives) and influences these metabolic pathways acting antagonistically to oncogenic Akt and c-Myc. Therefore PPAR α can be regarded as a candidate target molec Read More

Cytotoxic drugs in cancer therapy are used with the expectation of selectively killing and thereby eliminating the offending cancer cells. If they should die in an appropriate manner, the cells can also release danger signals that promote an immune reaction that reinforces the response against the cancer. The identity of these immune-enhancing danger signals, how they work extra- and intracellularly, and the molecular Read More

Treatment of cancer is by no means universally successful and often manifests harmful side effects. The best way to improve the success rate and reduce the side effects would be to develop compounds that are able to kill cancer cells while leaving normal cells unaffected. In this respect, mitocans (an acronym from ‘mitochondria’ and ‘cancer’), a summary term we proposed for compounds that induce cell death by target Read More