The protein-polysaccharide complex Venetin-1 from earthworm coelomic fluid as a potential natural remedy in the fight against yeast infections and human lung cancer

The human body functions efficiently thanks to the synchronised work of many vital cells. However, during our lifetime, each of them is exposed to numerous infections and cell changes like cancer. Resistance of human pathogens and cancer cells to commonly used therapies is also increasingly observed. That is why it is essential to constantly search for substances of natural origin, that allow for the strengthening or targeting of modern therapies.

Among the many natural compounds with great potential, preparations of earthworm origin attract attention. They have been used in therapy in Asia since ancient times as powders, liquid extracts of dried earthworms or pastes. Currently, research has confirmed antimicrobial, proteolytic, hemolytic, hemagglutinating, antifungal, and antitumor properties of the coelomic fluid (CF) naturally filling the body cavity of the earthworm. The problem is the toxicity of CF to the vertebrate cells. It turns out that the processing of the fluid associated with heating for a short time at 70°C changes the toxic properties of the CF. It becomes non-toxic to normal cells. We characterized the processed CF under the name Venetin 1 in terms of composition and biological activity. Using proteomic techniques, the protein composition of the preparation was characterized, which showed the presence of proteins from the lysenin, lysozyme group and sugars. Venetin 1 exhibits documented anti-fungal and anti-cancer activity. Proteomics studies conducted on Candida albicans cells and cancer cell lines (A549) using the SWATH-MS approach showed the proteome changes in both cases. In the case of Candida albicans cells, Venetin 1 showed effects on the cell wall and on mitochondria, activating the processes of apoptosis and autophagy. The lung cancer line A549 strongly responds to its presence by overexpressing proteins related to the activity of the mitochondrion and the endoplasmic reticulum and decrease of the levels of proteins associated with glycolysis/gluconeogenesis. The reduced expression of several proteins associated with radio-sensitization and chemotherapy of cancer cells was also observed.

Studies conducted on mice treated with cyclophosphamide have shown that sequential administration of CPAm and Venetin 1 positively affects lung tissue. Proteomic analysis showed activation of processes related to regeneration, autophagy, and anti-inflammatory processes in the mouse lung tissue. There is also an apparent effect on the pathways related to Rho GTPases and the activation of the complement system.

The presented results provide grounds for further research into using Venetin 1 as a preparation in the fight against candida infections and as a potential support in the treatment of lung cancer in humans.

Our thanks go to the OPUS19 grant from the National Science Center in Poland, the project 2020/37/B/NZ7/00763, UMO-2020/37/B/NZ7/00763.