Social wasp Polybia paulista defends itself against predators by producing a venom known to contain powerful cancer-fighting ingredients. Research published September 1 in the Biophysical Journal reveals how the toxin found in the venom–called MP1 (Polybia-MP1)–selectively kills cancer cells while not hurting healthy ones. On the surface of cancer cells, MP1 interacts with lipids that are abnormally distributed, creating a gaping hole through which molecules crucial to the cell’s function can pass. Paul Beales, co-senior study author at the University of Leeds in the UK, says treating cancer with drugs that target the cell membrane’s lipid composition would be an entirely new class of anticancer drugs. The findings should aid in the development of combination therapies that attack different parts of a cancer cell at the same time. MP1 works by disrupting the bacterial cell membrane, so it can be used for treating microbial diseases. In a surprising find, the antimicrobial peptide appears to prevent cancer in humans Cells of prostate and bladder cancer, as well as leukemia cells resistant to chemotherapy and other drugs, may be inhibited by this compound. MP1 selectively destroys cancer cells without harming normal cells, but the precise mechanism of this has not been identified until now. A large number of cancer cell managers, including Beales and Joo Ruggiero Neto of the So Paulo State University in Brazil, suspect that the reason for the difference might be associated with Healthy cell membranes consist of phospholipids known as phosphatidylserine (PS) and phosphatidylethanolamine (PE) located inside the inner leaflet of the membrane. PS and PE are not embedded in intact PS membranes, but are embedded in the outer membrane leaflets facing the surrounding cells. They tested their theory by fabricating model membranes and exposing them to MP1 in the presence of PE, PS, and water. The researchers investigated the destructive effects of MP1 on membranes using a wide array of imaging and biophysical techniques. PS increased MP1’s binding to the membrane by a factor of 7 to 8, in spite of not being bound to the membrane by PS. MP1, however, made holes of a magnitude of 20 to 30 larger due to the presence of PE, thereby enhancing the ability of MP1 to disrupt the membrane rapidly.
Neto says the pores are large enough that they allow molecules of critical importance like RNA and proteins to easily escape cells after being formed in only seconds. In future studies, the researchers plan to alter MP1’s amino acid sequence to examine how the structure of the peptide relates to its function and further enhance the peptide’s potency and selectivity for clinical use. The understanding of the mechanism of action of this peptide could help in translational studies to evaluate the potential of this peptide as a potential medicine. According to the investigation, since it has been shown that this peptide is selective towards cancer cells and non-toxic to normal cells in the lab, it likely has the potential to be safe, but further research is needed to prove that.