Introduction: Cancer is a disorder in which some body cells grow uncontrollably due to genetic changes and spread to other parts of the body. Tumor suppressor genes are genes that limit the rate of cell division, control the time of cell death, correct DNA mistakes, and limit the growth rate of a cell and protect it from cancer. The mutation of these tumor suppressor genes can allow the cell to grow out of control and lead to tumor and cancer. The most common tumor suppressor gene that is mutated in cancer patients is P53 or TP53. In more than half of cancers, this gene is lost or damaged and turned into an oncogene. Oncogenes can turn a healthy cell into a cancer cell.
Methods: Researchers have gained a lot of information about how genes play a role in cancer. But many cancers are not related to a particular gene, and often not just one gene, but several genes are involved in causing cancer. What is discussed in this review article is TP53 and its neighboring gene called POLR2A. Studies have shown that the mutation and deletion of TP53 in cancer cells leads to the mutation and deletion of POLR2A due to the proximity and in this case the number of copies of POLR2A is reduced and drugs and toxins such as alpha-Amanitin (α-AMA), which is obtained from a type of poisonous mushroom called Amanita phalloides, will have a greater effect on cancer cells than normal cells. Mushrooms and their products play an important role in global trade as an important dietary component and are rapidly becoming an essential part of the world's diet. However, due to the popularity of fungi, thousands of cases of poisoning occur worldwide annually. Among them, the most toxic fungi are those containing amanitins (AMAs). α-AMA is a bicyclic octapeptide and a strong inhibitor of DNA-dependent RNA polymerase II, which inhibits RNA polymerase II by blocking the transfer of RNA and DNA.
Results: It can be said that this unique mechanism of destruction, which basically acts on rapidly growing cells and ultimately leads to cell death, is almost more distinct and effective in alpha-Amanitin than other toxic cargoes produced in a laboratory.
Conclusion: A low and safe dose of this toxin can be used for cancer treatment, so that in this low dose, normal cells are less damaged, and by injecting a weak dose of this toxin, a suitable treatment can be created for cancer patients. With these findings, this research can provide a new perspective for the treatment of cancer using molecular and genetic methods and fungal toxins, and it is hoped that it will promise a new and long life treatment for cancer patients.
Keywords: POLR2A _ TP53_ Cancer_ alpha-Amanitin _ RNA polymerase II