Researchers from the University of Freiburg have discovered that the molecular mechanism of a toxin present in fish could be used in the future as medication for cancer treatment. Their research was published in the “Nature Communications” journal.
The pathogens species of Yersinia are responsible for causing the bubonic plague and other serious gastrointestinal infections in humans. Prof. Dr. Klaus Aktories and his team of researchers (including pharmacologist Prof. Dr. Thomas Jank) at the Institute of Experimental and Clinical Pharmacology and Toxicology at the University of Freiburg have studied a pathogen from Yersinia family called Yersinia Ruckeri.
This pathogen is also responsible for causing redmouth disease in the Salmonidae including the fishes salmon and trout, which has caused considerable financial losses to the fish industry.
The molecular mechanism involved
The researchers have discovered a toxin injection machine in the Y. Ruckeri genome. This machine structurally resembles viruses normally attacking the bacteria. It is demonstrated that the Afp 18 toxin present in the injection machine is an enzyme that causes deactivation of a switch protein called RhoA.
RhoA is involved in many important processes going on in the cells of fish and humans. For example, it manages the synthesis and breakdown of actin filaments. The actin filaments are important not only in cell division, but they also play a role in the metastasis and cancer spread throughout the body.
In association with the developmental biologist Prof. Dr. Wolfgang Driever, who is also from the University of Freiburg, the team of researchers have injected the Afp 18 toxin into the embryos of zebrafish. This has resulted in the blockage of cell division and has also hampered the development of zebrafish embryos.
The actin filaments present in fish are collapsed due to the toxin. This is due to the attachment of the toxin Afp 18 to the sugar molecule (N-acetylglucosamine) onto the Amino acid tyrosine present in the RhoA protein. Scientists consider it as an unusual natural reaction.
This mechanism becomes more clear at the atomic level by doing an X-ray analysis of RhoA crystals which are Afp 18 modified. This was done in association with Prof. Dr. Daan Von Aalten from the University of Dundee in Scotland.
The regulatory proteins of Rho are responsible for the cancer growth and metastasis. This reason has led the researchers from the University of Freiburg to believe that this fish toxin contains excellent therapeutic properties which are beneficial in the treatment of cancer.