Researchers at the University of Freiburg have noticed that the mechanism of action of a toxin present in fish can be utilized in cancer treatment. The “Nature Communications” Journal published their research work indicating the possible introduction of this toxin in the market as a commercial formula.
Certain pathogenic species of Yersinia can cause bubonic plague and other intestinal diseases in animals including humans. A team of researchers at the Institute of Experimental and Clinical Pharmacology and Toxicology at the University of Freiburg headed by Prof. Dr. Klaus Aktories and renowned pharmacologist Prof. Dr. Thomas Jank studied a pathogenic species of Yersinia known as Yersinia Ruckeri.
The bacteria can reside and multiply in the Salmonidae family including salmon fish and trout. Infection of these fish species with Yersinia is known as the redmouth disease which may occur in epidemic form and cause huge economic loss.
The pathogenesis of Y. Ruckeri
There is toxin injection machinery in the Y. Ruckeri cells. Structurally this machine is similar to bacteriophage ( a virus that infects and replicates within a bacterium). The injection machine contains Afp 18 toxin which is basically an enzyme involved in deactivation of a switch protein known as RhoA.
Although the exact role of RhoA is unknown, it is believed to be involved in many intracellular processes. It has been found to regulate the turnover of actin filaments which are important components of cell skeleton. Actin filaments also play an active role in cell division and thus growth and spread of tumor in the body.
The team of researchers at the University of Freiburg injected the Afp 18 toxin into the embryos of zebrafish under the supervision of a developmental biologist, Prof. Dr. Wolfgang Driever. They observed that arrested cell division in the zebrafish embryos resulted in their delayed development and growth.
The toxin caused aggregation of the actin filaments in the fish embryo. The molecular mechanism involves inactivation of the RhoA protein by attachment of the toxin to the sugar moiety N-acetylglucosamine of the Amino acid tyrosine. It is a unique natural phenomenon observed for the first time.
In-depth analysis of Afp 18 treated RhoA crystals was done by doing an X-ray scan. Prof. Dr. Daan Von Aalten from the University of Dundee in Scotland conducted this molecular level study.
Rho proteins play an important role in cancer cell growth and spread by regulating cell division. The findings of this research have opened the door to the possible therapeutic application of Salmonid Fish Toxin in cancer treatment. However, more research is needed to make safe and effective use of this toxin in humans.
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