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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