Toxic Peptide from Wasp Venom Targets Cancer Cell Membrane Phospholipids
By LabMedica International staff writers Posted on 15 Sep 2015 |
Image: The Brazilian social wasp Polybia paulista is the source of the Polybia-MP1 anticancer peptide (Photo courtesy of Dr. Mario Palma, Sao Paulo State University).
A toxic peptide component of the venom produced by a South American wasp effectively destroys some types of cancer cells through interactions with groups of phospholipids that are distributed abnormally on their cell membranes.
The Brazilian wasp Polybia paulista produces the bioactive host-defense peptide Polybia-MP1 (MP1) that has known anticancer properties. Its ability to poke holes in cancer cell membranes has been attributed to excess phosphatidylserine (PS) and phosphatidylethanolamine (PE) on the outer membrane of cancer cells. Normal cells, which do not have PS or PE exposed on the cell surface, are not damaged by exposure to MP1.
Investigators at the University of Leeds (United Kingdom) and their collaborators at Sao Paulo State University (Brazil) studied the mode of action of MP1 by creating a series of model membranes with PE and PS distributed in a various patterns internally and externally. They used a combination of membrane permeability assays and imaging techniques in this endeavor.
Results published in the September 1, 2015, issue of Biophysical Journal revealed that PS lipids significantly enhanced the bound concentration of MP1 peptide on the membrane by a factor of seven to eight. Furthermore, a combination of membrane permeability assays and imaging techniques showed that PE significantly increased the susceptibility of the membrane to disruption by MP1 and caused an order-of-magnitude increase in membrane permeability by facilitating the formation of larger transmembrane pores.
Atomic-force microscopy imaging revealed differences in the pore formation mechanism with and without the presence of PE. With PE present, MP1 was more effective at disrupting the membrane, increasing the size of holes that it caused by a factor of 20 to 30. Therefore, PS and PE lipids synergistically combined to enhance the formation of membrane pores by MP1, implying that the combined enrichment of both these lipids in the outer membranes of cancer cells was highly significant for MP1’s anticancer action.
"Formed in only seconds, these large pores are big enough to allow critical molecules such as RNA and proteins to easily escape cells," said contributing author Dr. Joao Ruggiero Neto, professor of biophysics at Sao 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."
"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," said senior author Dr. Paul Beales, senior research fellow in structural molecular biology at the University of Leeds. "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."
Related Links:
University of Leeds
Sao Paulo State University
The Brazilian wasp Polybia paulista produces the bioactive host-defense peptide Polybia-MP1 (MP1) that has known anticancer properties. Its ability to poke holes in cancer cell membranes has been attributed to excess phosphatidylserine (PS) and phosphatidylethanolamine (PE) on the outer membrane of cancer cells. Normal cells, which do not have PS or PE exposed on the cell surface, are not damaged by exposure to MP1.
Investigators at the University of Leeds (United Kingdom) and their collaborators at Sao Paulo State University (Brazil) studied the mode of action of MP1 by creating a series of model membranes with PE and PS distributed in a various patterns internally and externally. They used a combination of membrane permeability assays and imaging techniques in this endeavor.
Results published in the September 1, 2015, issue of Biophysical Journal revealed that PS lipids significantly enhanced the bound concentration of MP1 peptide on the membrane by a factor of seven to eight. Furthermore, a combination of membrane permeability assays and imaging techniques showed that PE significantly increased the susceptibility of the membrane to disruption by MP1 and caused an order-of-magnitude increase in membrane permeability by facilitating the formation of larger transmembrane pores.
Atomic-force microscopy imaging revealed differences in the pore formation mechanism with and without the presence of PE. With PE present, MP1 was more effective at disrupting the membrane, increasing the size of holes that it caused by a factor of 20 to 30. Therefore, PS and PE lipids synergistically combined to enhance the formation of membrane pores by MP1, implying that the combined enrichment of both these lipids in the outer membranes of cancer cells was highly significant for MP1’s anticancer action.
"Formed in only seconds, these large pores are big enough to allow critical molecules such as RNA and proteins to easily escape cells," said contributing author Dr. Joao Ruggiero Neto, professor of biophysics at Sao 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."
"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," said senior author Dr. Paul Beales, senior research fellow in structural molecular biology at the University of Leeds. "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."
Related Links:
University of Leeds
Sao Paulo State University
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