While most may view wasps as organisms derived from nature’s sadistic division that engineered the perfect stinging machine, many scientists have been preoccupied with the venom produced by a particular Brazilian wasp species called Polybia paulista.
Researchers from the University of Leeds, U.K. and São Paulo State University, Brazil have teamed up to study how a toxin in the wasp’s venom—called Polybia-MP1—is able to selectively kill cancer cells without harming normal cells. The investigators believe the answer lies with how MP1 interacts with lipids that are abnormally distributed across the surface of cancer cells.
“Cancer therapies that attack the lipid composition of the cell membrane would be an entirely new class of anticancer drugs,” explained co-senior author Paul Beales, Ph.D, senior translational research fellow at the University of Leeds. “This could be useful in developing new combination therapies, where multiple drugs are used simultaneously to treat cancer by attacking different parts of the cancer cells at the same time.”
The findings from this study were published recently in Biophysical Journal through an article entitled “PE and PS Lipids Synergistically Enhance Membrane Poration by a Host-Defense Peptide with Anticancer Properties.”
Previous works has shown that MP1 was able to disrupt bacterial pathogens by perturbing the microbial cell membrane, in addition to inhibiting the growth of certain types of cancer cells, such as prostate, bladder, and multi-drug resistant leukemia. However, until the present study, scientists were unclear as to how MP1 was able to leave normal cells unscathed and only selectively destroy the cancer cells.
Based off of the previous studies, the researchers surmised that the unique properties of cancer cells were a major factor for MP1 activity. Typically, normal healthy cell membranes are comprised of the phospholipids phosphatidylserine (PS) and phosphatidylethanolamine (PE), which are located within the inner membrane that faces the inside of the cell. However, for cancer cells, PS and PE are flipped to the outer surface.
Dr. Beales and his collaborators created model membranes containing PE and/or PS and exposed them to the MP1 toxin. They found that the presence of PS increased the binding of MP1 almost 8 fold, while the presence of PE enhanced MP1's ability to disrupt the membrane, increasing the pore size it created by a factor of 30.
“Formed in only seconds, these large pores are big enough to allow critical molecules such as RNA and proteins to easily escape cells,” stated co-senior author João Ruggiero Neto, Ph.D., professor at São Paulo State University. “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.”
Future plans have the researchers focused on altering the sequence of MP1 in order to obtain an even greater understanding of the peptide’s selectivity and potency, especially for use in clinical studies.
“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 noted. “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.”