In the pursuit of novel therapies for cancer, melittin has emerged as a potent possibility. Melittin is a peptide found in honey bee venom and has demonstrated a variety of biological and pharmacological applications (Jeong et al. 2014; Kohno et al. 2014). It has natural anti-bacterial, anti-viral, and anti-inflammatory properties (Jeong et al. 2014; Kohno et al. 2014). It has also shown a variety of anticancer properties across several different kinds of cancer including gastric (Mahmoodzadeh et al. 2013; Mahmoodzadeh et al. 2015), breast (Jeong et al. 2014; Jo et al. 2012), ovarian (Jo et al. 2012; Liu et al. 2013), liver (Chun-Yu et al. 2015; Wu et al. 2015), esophageal (Zhu et al. 2014), head and neck neoplasms (Yang et al. 2014), prostate (Jo et al. 2012), cervical (Jo et al. 2012), and lung cancer (Oh et al. 2014).
The anticancer properties of melittin seem to vary between different kinds of cancer. The ways in which the melittin impacts cancer cells represent many possibilities for its therapeutic uses in cancer. Melittin can inhibit cell proliferation (Jeong et al. 2014; Liu et al. 2013), induce apoptosis (Gajski & Garaj-Vrhovac 2013; Jeong et al. 2014; Mahmoodzadeh et al. 2013; Mahmoodzadeh et al. 2015), and cause necrosis in cancer cells (Mahmoodzadeh et al. 2013; Mahmoodzadeh et al. 2015). The mechanism of apoptosis appears related to the activation of the caspase-dependent pathway (Gajski & Garaj-Vrhovac 2013; Jo et al. 2012; Mahmoodzadeh et al. 2015). Necrosis emerges from damage to the cell membranes through necrotic cytotoxicity, as has been observed in rat thymocytes, murine skeletal muscle cells, GI tumour cells, erythrocytes, lymphocytes, lymphoblastoid cells, rat primary alveolar cells, and Caco-2 cells (Gajski & Garaj-Vrhovac 2013; Mahmoodzadeh et al. 2015).
Melittin can also cause cell cycle arrest and inhibit proliferation and growth (Gajski et al. 2016; Gajski & Garaj-Vrhovac 2013). Melittin can contribute to the prevention of angiogenesis through its ability to suppress EGF-induced VEGF secretion and inhibits the creation of new blood vessels by influencing HIF-1a (Shin et al. 2013) and via the prevention of activation of STAT3 and JAK2, critical elements of angiogenesis (Jo et al. 2012). Melittin can also prevent EGF-induced cell invasion through its reduction of the PI3K/Akt/mTOR signaling pathway, but this is primarily related to breast cancer cells (Jeong et al. 2014). In hepatocellular carcinoma melittin appears to inhibit cell proliferation through its influence on methyl-CpG binding protein 2 (MeCP2), which is a critical element in tumour growth and development (Wu et al. 2015). Melittin accomplishes this influence through a delay in G0/G1 cell cycle progression, which it is able to accomplish without causing apoptosis (Wu et al. 2015). In these few examples, it should become clear that melittin can affect cancer cells in a variety of ways.
It is worth noting that the common honey bee, Apis mellifera, has thus far been the most common source of melittin (Jeong et al. 2014). Recently Mahmoodzadeh et al. (2015) attempted to isolate melittin from the venom of Iranian honey bee, Apis mellifera meda, to determine its effects vis-à-vis cancer cells. The researchers discovered that the anticancer properties of the Iranian honey bee are similar to those of the common honey bee (Mahmoodzadeh et al. 2015). They also concluded that their findings confirmed earlier findings related to the anticancer properties of melittin, affirming that the effects of melittin on cancer cells is directly related to the cell type being affected and the amount of toxin (Mahmoodzadeh et al. 2015).
The greatest concerns regarding the use of melittin in cancer treatment is that it can also damage normal, healthy cells and that with regard to cancer treatment apoptosis is preferable to necrosis since necrosis can lead to systemic inflammation (Mahmoodzadeh et al. 2015). Like many cancer therapies, the damage to healthy cells is lamentable, so finding a means of delivery directly to the cancerous cells is preferable. The use of nanotechnology holds promise for such controlled delivery of melittin with positive implications for treatment (Misra et al. 2015).
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