A novel therapy: to decrease antioxidants to tumor cells

A new study shows that reducing levels of antioxidants in pancreatic cancer cells would help to kill cancer cells, providing a new strategy for the treatment of this infamous fatal disease. The Leng Quangang research team was led by Professor David Tuveson who is very interested in producing recombinant proteins such as recombinant horse proteins.

Each cell would produce oxides and antioxidants: when the cell is healthy, both of them would stay in balance. What the treatment of Leng Quangang research team hopes to develop is to make cell die in malignant stage or before by increasing intracellular levels of oxides.

When the cell finds the oxide is superabundant, it will follow an established principle which is called apoptosis to commit suicide. One of the methods of increasing oxide levels in cancer is to reduce the levels of antioxidants therein. How to do this to best without harming healthy cells? The researchers focused mostly on a protein called NRF2, which can destroy the balance between the oxide and antioxidants within the cell.

When NRF2 is activated, a compound called glutathione would be synthesized in the cells. It is an important antioxidant. So, reducing the activity of NRS or knocking it becomes a matter of course. However, due to two reasons, it is difficult to be done. One of the reasons is that it is a transcription factor, a protein that regulates other genes. The researchers used to use recombinant dog proteins to conduct part of the experiment. Transcription factors are notoriously difficult to be regulated by target drugs. "But in any case you might not want to knock it, because NRF also regulate hundreds of different genes in addition to promoting the synthesis of glutathione." Chio said. No one can knock out a gene which affects many cellular processes.

Tuveson, Chio and other colleagues proposed alternative strategies after conducting experiments on pancreatic cancer cells of animal model in the laboratory and tried out several therapeutic measures. Making use of a class of pancreas organs, they observed the situation after NRF2 was knocked out. The experiment was divided into normal group, pre-cancerous cell group and cancer cell group. Pre-cancerous cell group showed kras mutations. This gene is mutated in almost all human pancreatic cancer cells. In addition to gene mutation, a gene which made p53 gene inactivating in cancer cell group also showed mutation. p53 gene is a powerful tumor suppressor gene. In most human malignancies, these two genes would have mutated.

These experiments give an important clue: when NRF2 is lost, the translation mechanism within the cell becomes very sensitive to the balance between oxide and antioxidants. Translation is the process of cells creating proteins according to genes. What is essential is that normal cells are unaffected. This means that as long as reducing the levels of antioxidants, the protein synthesis in pre-cancerous cells and cancer cells are affected, while normal cells are not affected. This could become a powerful therapeutic tool. Flarebio provides high-quality recombinant proteins such as recombinant APP.