Nutritional starvation therapy is under intensive investigation because it provides a potentially lower toxicity with higher specificity than conventional cancer therapy. Autophagy, often triggered by starvation, represents an energy-saving, pro-survival cellular function; however, dysregulated autophagy could also lead to cell death, a process distinct from the classic caspase-dependent apoptosis.
A recent study shows how arginine starvation specifically kills tumor cells by a novel mechanism involving mitochondria dysfunction, reactive oxygen species generation, DNA leakage, and chromatin autophagy, where leaked DNA is captured by giant autophagosomes.
Cells when stressed, whether cancerous or not, undergo a process of cellular suicide that involves controlled dismantling of its interior components such as proteins, DNA, and various compartments. By far the most famous of such processes is “apoptosis”. The authors in this study have found another, distinct process involving mitochondria dysfunction, reactive oxygen species (ROS) generation, DNA leakage, and chromatin autophagy.
The senior author, Professor Hsing-Jien Kung, both a cancer biology at UC Davis and the Director of the National Health Research Institutes in Taipei, Taiwan, first discovered in 2009 the basic mechanism by which arginine shortage kills cancer cells.
“Traditional cancer therapies involve ‘poisoning‘ by toxic chemicals or ‘burning‘ by radiation cancer cells to death, which often have side effects,” according to Professor Kung. “An emerging strategy is to ‘starve’ cancer cells to death, taking advantage of the different metabolic requirements of normal and cancer cells. This approach is generally milder, but as this study illustrates, it also utilizes a different death mechanism, which may complement the killing effects of the conventional therapy.”
Via Dr. Stefan Gruenwald