Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy

Rady, Islam; Siddiqui, Imtiaz A.; Rady, Mohamad; Mukhtar, Hasan

doi:10.1016/j.canlet.2017.05.010

Cited by 300 publications

(275 citation statements)

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“…The successful use of the membrane‐active lipopeptide antibiotics daptomycin and telavancin in clinical medicine indicate that selectivity toward bacterial membranes is possible . Infact, a highly hemolytic peptide such as melittin is used for killing cancer cells by use of hydrogels . Unlike model peptides that may exhibit immune response on fatty acylation, host‐defense peptides such as cationic segments of defensins are not likely to elicit immune responses and could be attractive candidates for development as therapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

Effects of increasing hydrophobicity by N‐terminal myristoylation on the antibacterial and hemolytic activities of the C‐terminal cationic segments of human‐β‐defensins 1–3

et al. 2018

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Analogs of the cationic C-terminal segments of human-β-defensins HBD1-3, Phd1-3 with a single disulfide bond, exhibited comparable antimicrobial activity that was salt sensitive. They did not show hemolytic activity. In this study, N-terminal myristoylation was carried out on Phd1-3 to examine whether increasing hydrophobicity would result in improved antibacterial activity. The antibacterial activity of the oxidized myristoylated peptides MPhd1-3 and their reduced forms MPhd1r-3r was determined. These peptides showed enhanced antibacterial activity as compared to Phd1-3, on mid-log phase and stationary phase of Staphylococcus aureus and Escherichia coli, except MPhd1r-3r that were inactive on stationary-phase E. coli. In the presence of 150 mm NaCl, MPhd1-3 showed activity against S. aureus. MPhd1and two exhibited activity against E. coli but MPhd3 was inactive. Zeta potential measurements indicated that MPhd1-3 were more effective in surface charge neutralization of bacteria as compared to Phd1-3. MPhd1-3 exhibited hemolytic activity to varying extents with MPhd1 being most hemolytic. The data indicate that myristoylation enhances antibacterial activity and modulates hemolytic activity to different extents. Apart from hydrophobicity, distribution of cationic residues in MPhd1-3 plays important roles for these activities.

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Section: Discussionmentioning

confidence: 99%

Effects of increasing hydrophobicity by N‐terminal myristoylation on the antibacterial and hemolytic activities of the C‐terminal cationic segments of human‐β‐defensins 1–3

et al. 2018

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“…In addition, honeybee venom contains many low molecular mass compounds such as sugars, amino acids, phospholipids, pheromones and biogenic amines [2]. Extensive research conducted in recent years has shown that satisfactory results may be achieved when using bee venom for various types of diseases such as arthritis [3], chronic pain [4], cancer [5] and atopic dermatitis [6]. The major component of bee venom is called melittin.…”

Section: Introductionmentioning

confidence: 99%

Melittin—A Natural Peptide from Bee Venom Which Induces Apoptosis in Human Leukaemia Cells

et al. 2020

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Bee venom is a very complex mixture produced and secreted by the honeybee (Apis mellifera). Melittin is a major component of bee venom that accounts for about 52% of its dry mass. A vast number of studies have been dedicated to the effects of melittin’s regulation of apoptosis and to the factors that induce apoptosis in various types of cancer such as breast, ovarian, prostate, lung. The latest evidence indicates its potential as a therapeutic agent in the treatment of leukaemia. The aim of our present study is to evaluate melittin’s ability to induce apoptosis in leukaemia cell lines of different origin acute lymphoblastic leukaemia (CCRF-CEM) and chronic myelogenous leukaemia (K-562). We demonstrated that melittin strongly reduced cell viability in both leukaemia cell lines but not in physiological peripheral blood mononuclear cells (PMBCs). Subsequent estimated parameters (mitochondrial membrane potential, Annexin V binding and Caspases 3/7 activity) clearly demonstrated that melittin induced apoptosis in leukaemia cells. This is a very important step for research into the development of new potential anti-leukaemia as well as anticancer therapies. Further analyses on the molecular level have been also planned (analysis of proapoptotic genes expression and DNA damages) for our next research project, which will also focus on melittin.

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“…Although, it is composed of a diverse range of proteins and peptides, melittin is the major protein and comprises about 50% (w/w) of dry bee venom (Gajski and Garaj-Vrhovac, 2013). Melittin has anti-analgesic, anti-inflammatory, and antimicrobial activities (Gajski and Garaj-Vrhovac, 2013;Lin et al, 2017;Rady et al, 2017;Shi et al, 2016). However, no reports of melittin on lung cancer proliferation and monocyte differentiation are available.…”

mentioning

confidence: 99%

Melittin Induced G1 Cell Cycle Arrest and Apoptosis in Chago-K1 Human Bronchogenic Carcinoma Cells and Inhibited the Differentiation of THP-1 Cells into Tumour- Associated Macrophages

Tipgomut

Wongprommoon

Takeo

et al. 2018

Asian Pac J Cancer Prev

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Background: Bronchogenic carcinoma (lung cancer) is one of the leading causes of death. Although many compounds isolated from natural products have been used to treat it, drug resistance is a serious problem, and alternative anti-cancer drugs are required. Here, melittin from Apis mellifera venom was used, and its effects on bronchogenic carcinoma cell proliferation and tumour-associated macrophage differentiation were evaluated. Methods: The half maximal inhibitory concentration (IC50) of melittin was measured by MTT. Cell death was observed by annexin V and propidium iodide (PI) co-staining followed by flow cytometry. Cell cycle arrest was revealed by PI staining and flow cytometry. To investigate the tumour microenvironment, differentiation of circulating monocytes (THP-1) into tumour-associated macrophages (TAMs) was assayed by sandwich-ELISA and interleukin (IL)-10 levels were determined. Cell proliferation and migration was observed by flat plate colony formation. Secretion of vascular endothelial growth factor (VEGF) was detected by ELISA. The change in expression levels of CatS, Bcl-2, and MADD was measured by quantitative RT-PCR. Results: Melittin was significantly more cytotoxic (p < 0.01) to human bronchogenic carcinoma cells (ChaGo-K1) than to the control human lung fibroblasts (Wi-38) cells. At 2.5 µM, melittin caused ChaGo-K1 cells to undergo apoptosis and cell cycle arrest at the G1 phase. The IL-10 levels showed that melittin significantly inhibited the differentiation of THP-1 cells into TAMs (p < 0.05) and reduced the number of colonies formed in the treated ChaGo-K1 cells compared to the untreated cells. However, melittin did not affect angiogenesis in ChaGo-K1 cells. Unlike MADD, Bcl-2 was up-regulated significantly (p < 0.05) in melittin-treated ChaGo-K1 cells. Conclusion: Melittin can be used as an alternative agent for lung cancer treatment because of its cytotoxicity against ChaGo-K1 cells and the inhibition of differentiation of THP-1 cells into TAMs.

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Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy

Cited by 300 publications

References 103 publications

Effects of increasing hydrophobicity by N‐terminal myristoylation on the antibacterial and hemolytic activities of the C‐terminal cationic segments of human‐β‐defensins 1–3

Effects of increasing hydrophobicity by N‐terminal myristoylation on the antibacterial and hemolytic activities of the C‐terminal cationic segments of human‐β‐defensins 1–3

Melittin—A Natural Peptide from Bee Venom Which Induces Apoptosis in Human Leukaemia Cells

Melittin Induced G1 Cell Cycle Arrest and Apoptosis in Chago-K1 Human Bronchogenic Carcinoma Cells and Inhibited the Differentiation of THP-1 Cells into Tumour- Associated Macrophages

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