Brazilian wasp venom kills cancer cells

The wasp Polybia paulista protects itself against predators by producing venom known to contain a powerful cancer-fighting ingredient. The venom's toxin called MP1 (Polybia-MP1)—selectively kills cancer cells without harming normal cells. MP1 interacts with lipids that are abnormally distributed on the surface of cancer cells, creating gaping holes that allow molecules crucial for cell function to leak out. This could be useful in developing new combination therapies, where multiple drugs are used simultaneously to treat a cancer by attacking different parts of the cancer cells at the same time. MP1 acts against microbial pathogens by disrupting the bacterial cell membrane. Serendipitously, the antimicrobial peptide shows promise for protecting humans from cancer; it can inhibit the growth of prostate and bladder cancer cells, as well as multi-drug resistant leukemic cells. However, until now, it was not clear how MP1 selectively destroys cancer cells without harming normal cells. In healthy cell membranes, phospholipids called phosphatidylserine (PS) and phosphatidylethanolamine (PE) are located in the inner membrane leaflet facing the inside of the cell. But in cancer cells, PS and PE are embedded in the outer membrane leaflet facing the cell surroundings. The presence of PS increased the binding of MP1 to the membrane by a factor of 7 to 8. On the other hand, the presence of PE enhanced MP1's ability to quickly disrupt the membrane, increasing the size of holes by a factor of 20 to 30. In future studies, the researchers plan to alter MP1's amino acid sequence to examine how the peptide's structure relates to its function and further improve the peptide's selectivity and potency for clinical 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.

Ref: Natália Bueno Leite, 2015, Biophysical Journal

dx.doi.org/10.1016/j.bpj.2015.07.033

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