Starving Cancer Cells to Death

Cancer is basically the inability of the body to control the division of its own cells. This is caused by mutations in the DNA of a cell that causes it to lose its normal identity in a tissue, ignore signals from surrounding cells, and grow abnormally.


Normally, a cell has to undergo a regulated series of events before dividing . When something unnatural in the cell is recognized, such as mutations,  a process called apoptosis  causes the cell to undergo programmed cell death allows by dismantling itself.

 

Ideally, it would make sense if the immune system would tell early cancer cells to dismantle themselves by apoptosis as soon as they begin to develop cancer-like characteristics. Unfortunately, mutations have arisen that allow the cancer cells to resist common apoptosis. To combat this, scientists historically used chemotherapy and radiation as a way to “poison” or “burn” the cells to death. As many know, these two methods come with many negative side effects such as nausea, pain, and fatigue. To overcome some of these side effects while still attacking the cancer cells, scientists are looking into a new form of therapy called chromatophagy.

The basic idea behind chromatophagy is to create an environment within the cell so that the organelles can’t function correctly. When this happens, the cell may undergo autophagy. During autophagy, an organelle called the lysosome digests worn out or dysfunctional organelles. This is not the same thing as apoptosis, but the end result is the same – without functioning organelles, the cell eventually dies.

One way of convincing a cell to undergo autophagy is to starve the cell of essential nutrients, such as amino acids. Researchers at UC Davis and the National Health Research Institutes in Taipei, Taiwan  have identified that by depriving the cells of the amino acid arginine that they are able to induce cell death. Without arginine, mitochondria (the powerhouses of the cell) become dysfunctional, and produce large amounts of oxidative compounds. These, in turn, damage the chromatin (proteins) and DNA in the cell,  and induce the process of autophagy. (The name chromatophagy is based on the damage to the chromatin and resulting autophagy). The end results is that the cancerous cell literally eats itself.  This method will allow scientists to kill cancer cells from the inside out without the harshness of chemicals. Early clinical trials are already underway for some forms of cancer.

Additional Resources:

  • Changou C.A., L. Xing, Y. Yen, F. Y. S. Chuang, R. H. Cheng, R. J. Bold, D. K. Ann & H.-J. Kung (2014). Arginine starvation-associated atypical cellular death involves mitochondrial dysfunction, nuclear DNA leakage, and chromatin autophagy, Proceedings of the National Academy of Sciences, DOI: http://dx.doi.org/10.1073/pnas.1404171111

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