by Rideeta Raquib
Antioxidants are natural chemicals found in food and tissue that may have beneficial health effects. Although it is a common ideology that antioxidants aid in fighting cancer, pancreatic cancer research at Cold Spring Harbor Laboratory (CSHL) begs to differ. In healthy cells, oxidizing and anti-oxidizing agents are maintained at a certain level of balance. The team at CSHL, led by Professor David Tuveson, M.D., Ph.D., explains that in malignant cells there is a rise in oxidizing agents, but there is also an increase in antioxidants which counter the level of oxidation. Tuveson and his team aimed to study whether reducing antioxidants would cause cancer cells to die from apoptosis due to excess oxidation.
The CSHL team focused on the state of the NRF2 gene, which is a key regulator between oxidation and reduction in cancer cells. An affinity tag was utilized to conduct a reaction with a reduced cysteine and mass spectroscopy was carried out in order to detect changes in the oxidation of cysteine, which is associated with the state of NRF2. An active NRF2 induces the production of glutathione, an essential antioxidant. Unfortunately, it is not possible to block the activity of this gene because NRF2 regulates other genes as a transcription factor. Researchers still proceeded with experiments to observe the effects of eliminating NRF2 in pancreatic cells sampled from pancreatic cancer patients and healthy individuals. It was discovered that an absent NRF2 in cancer cells affected the equilibrium between oxidants and antioxidants within the machinery responsible for protein synthesis in. It was also found that there was no impact on protein synthesis in the healthy pancreas cells.
An AKT inhibitor, which inhibits protein synthesis, and BSO, an inhibitor of glutathione, antioxidant synthesis, can be combined to mimic the absence of NRF2. This technique was tested on mice and had remarkable results. Administering AKT inhibitor solely proved to be harmful, but when both components were combined, the AKT did kill cancer cells effectively, while normal pancreas cells were not affected. Overall, the experiment shows support that pancreatic cancer cells could be eradicated more adequately when levels of antioxidants are reduced. More studies are currently underway, in which scientists are taking this new finding and incorporating various translation inhibitors and repressors to find the perfect treatment option for patients in the future.
- I.C. Chio, et al., NRF2 promotes tumor maintenance by modulating mRNA translation in pancreatic cancer. ScienceDirect (2016). doi: 10.1016/j.cell.2016.06.056.
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