The Brazilian social wasp defends itself with a venom containing an antimicrobial peptide that has been identified as having anticancer properties.
Image credit: Prof. Mario Palma/Sao Paulo State University
Venom belonging to the Brazilian social wasp Polybia paulista contains the antimicrobial peptide Polybia-MP1 (MP1), which has been demonstrated to inhibit multiple forms of cancerous cells such as prostate cancer, bladder cancer and multidrug-resistant leukemic cells.
Despite this antimicrobial peptide showing great potential as a component of anticancer treatment in humans, researchers have not fully understood exactly how MP1 kills cancer cells.
The new study, published in Biophysical Journal, now reveals how MP1 is capable of killing cancer cells while leaving normal cells unscathed: by attacking lipids on the surface of cancer cells and creating holes that allow important cell molecules to leak out.
"Cancer therapies that attack the lipid composition of the cell membrane would be an entirely new class of anticancer drugs," explains study co-senior author Paul Beales of the University of Leeds in the UK.
"This could be useful in developing new combination therapies," he adds, "where multiple drugs are used simultaneously to treat a cancer by attacking different parts of the cancer cells at the same time."
The researchers hypothesized that the mechanism behind MP1's effectiveness against cancer cells would involve the way that cancer cell membranes differ from healthy cell membranes.
One major difference is the positioning of two lipids that form part of the cell membrane: phosphatidylserine (PS) and phosphatidylethanolamine (PE). In cancer cells, PS and PE are located in the outer cell membrane facing outward from the cell, while in healthy cells, they are situated in the inner membrane and face inward.
MP1 creates pores large enough for critical molecules to easily escape cancer cells
To test their hypothesis, the researchers created some model cell membranes. Some of these contained PS, some contained PE and some contained both. They then exposed their model membranes to MP1 and observed what happened.
Using a combination of membrane permeability assays and imaging techniques, the researchers revealed that PS increased the binding of the antimicrobial peptide to the cell membrane, while the presence of PE boosted MP1's ability to quickly disrupt the membrane and increase the size of any holes in it.
The formation of these holes was key to how MP1 kills cancer cells, as co-senior author João Ruggiero Neto, of São Paulo State University in Brazil, explains:
"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 permeabilization induced by the peptide in the presence of PE and the dimensions of the pores in these membranes was surprising."
Going forward, the researchers plan to experiment with adjusting MP1's amino acid sequence, enabling them to investigate how MP1's structure relates to its function, as well as potentially boosting 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," Dr. Beales concludes. "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."
Wasps are not the only creatures that have certain characteristics which could benefit human health. In a Spotlight feature published earlier this year, Medical News Today examined how spiders, bees, scorpions, frogs, Gila monsters and snakes could provide novel forms of treatment for human conditions.