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According to a new study carried out by some researchers from the University of Texas MD Anderson Cancer Center, the toxin of some poisonous mushrooms can be used to treat some types of cancer. Researchers said that the alpha-amanitin (a toxin) extracted from the “death cap” mushroom has a potential of cancer treatment. However, it has a tendency to cause liver toxicity that has limited its use as an effective cancer therapy.
Researchers carried out an analysis of antibody-drug conjugates based on the alpha-amanitin. They found that it is a highly effective treatment of colorectal cancer in the mouse. They found this drug caused a complete regression of the tumor with effectively reduced liver toxicity.
An associate professor of cancer biology, Xiongbin Lu observed that when TP53 (a gene that encodes for tumor suppressor protein) is deleted from the chromosome that is responsible for the cancer growth, a nearby gene POLR2A (a gene encoding the largest subunit of the RNA polymerase II) is also deleted. Lu targeted cancers that contained a single copy of both genes (normal cells contain two copies of both genes) representing 53 percent colorectal cancers, 75 percent ovarian cancers and 62 percentage breast cancers. Lu said that POLR2A gene is an essential for cell survival. Because there is only one copy of both genes, the cancer cells are more susceptible of the suppression of this gene.
Discovery of the fact that POLR2A is also deleted along with the TP53 has provided a new way of treating cancer. As a single copy of POLR2A can allow cancerous cells to grow and, therefore, can be a new target to hit. As POLR2A turns out, it can be suppressed by the ADC based mushroom toxin. Lu said that TP53 based cancer therapy was not successful because of the complexity of TP53 signaling. However, alpha-amanitin can inhibit product of the POLR2A gene, therefore, there is no RNA Pol II to transcribe genes and thus cancerous cells can be controlled. They also found that suppression of POLR2A with the low dose of alpha-amanitin can stop the cancerous cell growth with reduced toxicity.
Reference: Nature Journal