The Brazilian social wasp Polybia paulista produces venom that may be cancer fighting. The wasps toxin, called MP1 will kill cancer cells and not harm normal cells. A cancer cell membrane has a different lipid composition than a normal cell and the venom destroys cancer cells because of this difference. The phospholipid bilayer of normal cells is asymetrical, so there are different types of phospholipids on the inner leaflet compared to the outer leaflet. One difference is the concentrations of phosphatidylserine (PS) and phosphatidylethanolamine (PE). Normal cells have these phospholipids on the inner leaflet of the membrane, while cancerous cells have them on the outside. PS will increase binding of MP1 to the membrane by a factor of about 8. The presence of PE in the outer membrane and MP1 causes membrane permeability to increase so much that RNA and other essential proteins escape out of the cell, causing the cell to become non-functional and die. This has shown promise for prostate and bladder cancer cells. I am unsure why it is only for these cancers, but this was very interesting. The first link is the news article and the second link is the research article regarding how PE and PS with MP1 destroy cancerous cells.
http://phys.org/news/2015-09-brazilian-wasp-venom-cancer-cells.html
http://www.cell.com/biophysj/abstract/S0006-3495(15)00768-7
In a study it was shown that PS is an important activator of several enzymes, including protein kinase C. Whereas PE appears to be involved in the correct folding of membrane proteins, especially in regulating lipid homeostasis via the sterol response element-binding protein. So if PE and PS were to translocate from the inner leaflet to the outer leaflet than the cell is prone to disruption of of enzyme phosphorylation and membrane protein folding. I wonder what specific mechanism of cancer is making PE and PS translocate to the outer leaflet.
ReplyDeletehttp://www.ncbi.nlm.nih.gov/pubmed/14604010