Wasp Venom Peptide Selectively Punctures Cancer Cell Membranes | September 7, 2015 Issue - Vol. 93 Issue 35 | Chemical & Engineering News
Volume 93 Issue 35 | p. 12 | News of The Week
Issue Date: September 7, 2015

Wasp Venom Peptide Selectively Punctures Cancer Cell Membranes

Drug Discovery: Peptide may target phospholipids when attacking tumor cells
Department: Science & Technology | Collection: Critter Chemistry, Life Sciences
News Channels: Biological SCENE
Keywords: wasp, cancer, peptide, cell membrane, biophysics
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The Polybia paulista wasp produces a peptide that punches holes in phospholipid bilayers. The size and number of holes depends on the bilayer composition, as shown in these atomic force micrographs.
Credit: Mario Palma/São Paulo State University/Cell Press
The peptide MP1 from the Polybia paulista wasp (top) selectively kills cancer cells by tearing pores in the cells’ membranes (bottom).
 
The Polybia paulista wasp produces a peptide that punches holes in phospholipid bilayers. The size and number of holes depends on the bilayer composition, as shown in these atomic force micrographs.
Credit: Mario Palma/São Paulo State University/Cell Press

Though few people would welcome a sting from the Brazilian wasp Polybia paulista, the wasp’s venom does contain a potentially useful molecule. The venom peptide MP1 selectively kills human cancer cells by creating pores in their membranes. Now researchers have found out why MP1 attacks tumor cells but not healthy ones.

The explanation suggests a possible new cellular structure to target when designing cancer drugs.

Research teams at São Paulo State University in Brazil and the University of Leeds in England determined that MP1’s selectivity arises from differences in the compositions of the phospholipid bilayers that make up healthy and cancer cell membranes (Biophys. J. 2015, DOI: 10.1016/j.bpj.2015.07.033). Tumor endothelial cells have large numbers of phospholipids called phosphatidylserine (PS) and phosphatidylethanolamine (PE) in the outer layer of their membranes; healthy cells do not.

To test whether MP1 targets this difference, the research groups created model membrane layers in solution composed of different combinations of phospholipids: one with just a common phospholipid called phosphatidylcholine (PC), one with PS and PC, one with PE and PC, and one with all three.

Using several types of imaging, including atomic force microscopy, researchers found that MP1 didn’t form pores in the PC-only membranes. The peptide bound to the PC/PS membrane, but the pores it made were small enough for the membrane to seal itself. The PC/PE membrane, on the other hand, created larger pores but in small quantities. Only with the PC/PE/PS membrane did MP1 produce pores numerous enough and severe enough to create leaks able to kill a cell.

The prevailing wisdom in drug development is that membrane lipids aren’t good drug targets because drug interactions with them are not specific, says Georg Pabst, professor of molecular biosciences at the University of Graz in Austria. “The present study nicely shows that interactions with membrane lipids are specific indeed.” Pabst, who was not involved in the study, says the researchers’ results “strongly nurture a change in paradigm in drug design.”

 
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Comments
Ernest Reid (September 14, 2015 5:47 PM)
A DNA Nano clew delivery system has been developed by researchers at NC State and UNC Chapel Hill. The wasp molecule could be delivered to cancer cells via the Nano clew. They delivered a protein PLEKHA7 to about 17 different cancer cells and that worked to make the kill
Hope others will follow up on this. I have a rare urethral cancer and will volunteer for any trials
Paul Akomeah (October 17, 2015 10:47 AM)
Wonderful
Hannah (January 22, 2016 6:54 PM)
Am I correct in thinking that whatever materials exit through the pores will be degraded by proteases and therefore unable to harm the body?
Maurice L. Payne (February 27, 2016 6:15 AM)
Early detection for prostate cancer diagnosis. Am I a canidate for clinical trail found in wasp venom research?

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