According to new research, venom from the Brazilian wasp can efficiently kill cancer cells while leaving the healthy cells intact. The findings revealed that the venom destroys cancer cells by creating gaping holes that allow molecules crucial for cell function to leak out, and scientists believe that this could be useful in the development of new anti-cancer therapies.
The study published in the Biophysical Journal discovered that the ingredient found in the venom of Polybia paulista (Polybia-MP1) destroys cancer cells without harming normal ones. So far, it hasn’t been known how the cancer-fighting toxin in the wasp, MP1 (Polybia-MP1), selectively eradicates cancer cells. But scientists from the University of Leeds and the São Paulo State University in Brazil found that MP1 disrupts the bacterial cell membrane to act against microbial pathogens explaining that this toxin actually acts on the atypical arrangement of fats, or lipids, in cancer cell membranes. It is this irregular dispersal of fats that creates weak points on the cell membrane where the toxin interacts with the lipids, creating gaping holes that are large enough for essential molecules, which are crucial for cell function, to start leaking out. It has been shown that MP1 successfully stops the growth of prostate and bladder cancer cells as well as multi-drug-resistant leukemic cells.
In the words of João Ruggiero Neto, one of the senior authors of the study: “Formed in only seconds, these large pores are big enough to allow critical molecules such as RNA and proteins to easily escape cells. The dramatic enhancement of the permeabilisation induced by the peptide in the presence of PE and the dimensions of the pores in these membranes was surprising.”
For one thing, MP1 targets two lipids— phosphatidylserine, or PS, and phosphatidylethanolamine, or PE—that cancer cells have on the outside of their membranes, unlike healthy cell membranes, which have these lipids located in the inner membrane leaflet facing the inside of the cell.
The researchers tested their theory by creating model membranes, some of which contained PE and/or PS, and exposing them to MP1. They used a wide range of imaging and biophysical techniques to characterize MP1’s destructive effects on the membranes. Strikingly, the presence of PS increased the binding of MP1 to the membrane by a factor of 7 to 8. On the other hand, the presence of PE enhanced MP1’s ability to quickly disrupt the membrane, increasing the size of holes by a factor of 20 to 30.
Paul Beales, also a senior study author, said: “Cancer therapies that attack the lipid composition of the cell membrane would be an entirely new class of anti-cancer drugs. This could be useful in developing new combination therapies, where multiple drugs are used simultaneously to treat a cancer by attacking different parts of the cancer cells at the same time.”
The researchers plan to further experiment with adjusting MP1’s amino acid sequence, which will help them to determine how MP1’s structure is linked to its function, along with potentially enhancing its anticancer properties for therapeutic purposes.
“Understanding the mechanism of action of this peptide will help in translational studies to further assess the potential for this peptide to be used in medicine. As it has been shown to be selective to cancer cells and non-toxic to normal cells in the lab, this peptide has the potential to be safe, but further work would be required to prove that.”