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The Use Of Melittin As An Anti Cancer Drug

1615 words - 6 pages

Over the centuries, the venom of animals has had its range of uses, from cosmetics to the treatment of various illnesses. Quite some years ago, there was a mortality study conducted on beekeepers, which showed that there was a slightly lower mortality incidence of cancer in beekeepers than in normal people [1]. This sparked and interest into the venom of honeybees (Apis meliffera) [2] and its effects on cancerous cells. Bee venom is used to treat a variety of conditions. One condition that seems to be most popular in all the research is cancer. Cancer is a condition widely known as the rapid and uncontrolled division of cells. The venom of bees contains a peptide called Melittin (MEL), a major constituent of bee venom [1] that has potential to work as an anti-cancer drug. It is unknown what is the major pathway in which this peptide works; however, scientists are discovering multiple pathways in which the peptide works. The main effects that MEL has on tumor cells are that it: causes cell cycle alterations, effects growth and proliferation and it also induces apoptosis [1]. This essay aims to review and evaluate the different pathways through which MEL targets and kills cancer cells.

Bee venom, like most venom, contains a very complex mixture of peptides. Aside from peptides, bee venom also contains enzymes such as phospholipase A2, lipids, carbohydrates and other biological amines [1]. Studies show that the majority of the bee venom is composed of MEL, phospholipase A2 (PLA2) and other small amino acids [1]. MEL is composed of 26 amino acids (NH2-Gly-Ile-Gly-Ala-Val-Leu-Lys-Val-Leu-Thr-Th-Gly-Leu-Pro-Ala-Leu-Ile-Ser-Trp-Ile-Lys-Arg-Lys-Arg-Gln-Gln-CONH2) [1] [3] forming two alpha helices creating an overall “bent-rod” shape [3]. The molecule is amphipathic and amphoteric with 20 hydrophobic, non-polar and neutral amino acids on the N-terminal, and the remaining 6 amino acids, which are polar and basic are located on the C-terminal [1].

Figure 1: Molecular structure of Melittin [1]

MEL, itself, has direct action on cells. The main way in which MEL kills cells is by forming pores with in the cell membrane, causing a disruption in the cell’s electrochemical potential gradient, causing the cell to lyse. The transient pores are formed due to the aggregation of 3-5 MEL peptides [4], and it is the assembly of the peptides, which form a wedge shape, which actually splits the lipid bilayer [4]. The peptides are adsorbed onto the bilayer surface and because of the high peptide to lipid ratio [4]; the peptides are able to penetrate the surface forming the pore. Formation of the pore is also due to the amphipathic nature of MEL [1]. What is great about this mechanism is the fact that, most cancer cells don’t develop a mechanism by which they are resistant to pore forming agents [1]. Tumor cells have a high membrane potential compared to normal cells [1], and due to the amphipathic structure of MEL, it preferentially likes to bind to cell membranes that...

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