ReviewMelittin: A lytic peptide with anticancer properties
Introduction
In recent decades, the number of cancer patients and their mortality has considerably increased, hence creating huge health and economic problems. The growing incidence of tumours brings about a need to explore new drugs and new strategies in treating this particular disease. This is why the studies on anticancer research and different possibilities of its treatment are one of the main tasks of modern science (Gotay, 2010, Stewart and Kleihues, 2003). Scientists are putting huge efforts in finding a cure for this disease because although today the prescribed therapy in the form of surgery, radiotherapy and chemotherapy helps patients to combat the disease, the results are still fatal to many people.
Despite significant advances of modern medicine, drugs derived from plants and animals continue to make a major contribution to health in terms of prevention and treatment of many diseases including cancer (Guilford and Pezzuto, 2008, Harvey, 1998, Harvey, 2000, Mehta and Pezzuto, 2002, Mehta et al., 2010). Many treatments often applied in Western medicine originate from Asia, and their popularity continues to grow (Graziose et al., 2010, Parekh et al., 2009). Poisonous animals, especially insects, have long been used in scientific research, and today represent the basis of many drugs widely used in medicine (Amin et al., 2009, Da Rocha et al., 2001, Lewis and Garcia, 2003, Nobili et al., 2009). Toxins from various animals such as those isolated from snakes, spiders, scorpions, sea urchins and corals have the ability to kill tumour cells (Borkow et al., 1992, Das Gupta et al., 2007, Debnath et al., 2007, Feofanov et al., 2005, Gao et al., 2007, Gomes et al., 2010, Meunier et al., 2000, Nagaraju et al., 2006, Nishioka et al., 2003, Pettit et al., 1981, Schweitz et al., 1985, Soletti et al., 2008, Soroceanu et al., 1998, Van Den Berg et al., 2002, Wang and Ji, 2005, Yang et al., 2005). Of the many natural compounds that are used in oriental and alternative medicine, toxins isolated from many organisms are the ones that have been used the longest; European honeybee Apis mellifera venom being the most extensively studied toxin (Cherniak, 2010, Gajski and Garaj-Vrhovac, 2008, Gajski and Garaj-Vrhovac, 2010, Gajski and Garaj-Vrhovac, 2011, Garaj-Vrhovac and Gajski, 2009, Oršolić, 2012, Son et al., 2007).
The use of bee products in the prevention and treatment of diseases is known as apitherapy. Usage of natural products and their active components for treating of different ailments is based primarily on the experience of traditional medical practice in different ethnic communities as well as in the epidemiological observations (Cherniak, 2010). Interest in the medicinal properties and especially anticancer effects of bee venom (BV) and its major constituent melittin (MEL) increased tremendously in the past few years; therefore the present paper brings an overview of recent researches on anticancer properties of the lytic peptide MEL, which is the main active component of whole BV.
Section snippets
Bee venom
BV is produced in the bee's venom gland in the abdominal cavity (Habermann, 1972). Venom itself is a very complex mixture of a variety of different active peptides, including MEL, apamin, adolapin and mast cell degranulating peptide (Dotimas et al., 1987, Eiseman et al., 1982, Hider and Ragnarsson, 1980, Shipolini, 1984). In addition, it also contains enzymes phospholipase A2 (PLA2) and hyaluronidase, biologically active amines and non-peptide components including lipids, carbohydrates and free
Melittin
MEL is the main component of BV and the principal toxin which constitutes approximately 50% of its dry matter. MEL is a small linear basic peptide with the chemical formula C131H228N38O32 consisting of the known 26 amino acid sequence, weighing 2847.5 Da, which has a powerful haemolytic activity (Fig. 1). Its amino acid sequence is Gly-Ile-Gly-Ala-Val-Leu-Lys-Val-Leu-Thr-Thr-Gly-Leu-Pro-Ala-Leu-Ile-Ser-Trp-Ile-Lys-Arg-Lys-Arg-Gln-Gln (Terwilliger and Eisenberg, 1982a, Terwilliger and Eisenberg,
Conclusions and future prospects
The above mentioned studies suggest that both BV and its major component MEL cause a strong toxic effect on different types of tumour cells such as kidney, lung, liver, prostate, bladder, breast, and leukemic cells, while this effect in normal cells is less pronounced. The proposed mechanism of action of BV and its peptide components are related to the activation of PLA2, caspase and matrix metalloproteinase that destroy tumour cells (Holle et al., 2003, Moon et al., 2006). Conjugation of MEL
Conflict of interest statement
The authors report no conflict of interest.
Acknowledgement
Supported by the Croatian Ministry of Science, Education and Sports (grant no. 022-0222148-2125).
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