Bee venom in cancer therapy

Department of Animal Physiology, University of Zagreb, Zagreb, Croatia.
CANCER AND METASTASIS REVIEW (Impact Factor: 7.23). 11/2011; 31(1-2):173-94. DOI: 10.1007/s10555-011-9339-3
Source: PubMed


Bee venom (BV) (api-toxin) has been widely used in the treatment of some immune-related diseases, as well as in recent times in treatment of tumors. Several cancer cells, including renal, lung, liver, prostate, bladder, and mammary cancer cells as well as leukemia cells, can be targets of bee venom peptides such as melittin and phospholipase A2. The cell cytotoxic effects through the activation of PLA2 by melittin have been suggested to be the critical mechanism for the anti-cancer activity of BV. The induction of apoptotic cell death through several cancer cell death mechanisms, including the activation of caspase and matrix metalloproteinases, is important for the melittin-induced anti-cancer effects. The conjugation of cell lytic peptide (melittin) with hormone receptors and gene therapy carrying melittin can be useful as a novel targeted therapy for some types of cancer, such as prostate and breast cancer. This review summarizes the current knowledge regarding potential of bee venom and its compounds such as melittin to induce cytotoxic, antitumor, immunomodulatory, and apoptotic effects in different tumor cells in vivo or in vitro. The recent applications of melittin in various cancers and a molecular explanation for the antiproliferative properties of bee venom are discussed.

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    • "Charge deconvoluted low-energy CID/ETD spectra are shown on Fig. 1. Identified peptides are in agreement with previous findings regarding peptide components of BV (Oršolić, 2012; Son et al., 2007). Additionally, the concentration of MEL in BV was determined (Fig. 2). "
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    ABSTRACT: In the present study, we investigated the possible combined anticancer ability of bee venom (BV) and cisplatin towards two pairs of tumour cell lines: parental cervical carcinoma HeLa cells and their cisplatin-resistant HeLa CK subline, as well as laryngeal carcinoma HEp-2 cells and their cisplatin-resistant CK2 subline. Additionally, we identified several peptides of BV in the BV sample used in the course of the study and determined the exact concentration of MEL. BV applied alone in concentrations of 30 to 60 µg ml–1 displayed dose-dependent cytotoxicity against all cell lines tested. Cisplatin-resistant cervical carcinoma cells were more sensitive to BV than their parental cell lines (IC50 values were 52.50 µg ml–1 for HeLa vs. 47.64 µg ml–1 for HeLa CK cells), whereas opposite results were obtained for cisplatin-resistant laryngeal carcinoma cells (IC50 values were 51.98 µg ml–1 for HEp-2 vs. > 60.00 µg ml–1 for CK2 cells). Treatment with BV alone induced a necrotic type of cell death, as shown by characteristic morphological features, fast staining with ethidium-bromide and a lack of cleavage of apoptotic marker poly (ADP-ribose) polymerase (PARP) on Western blot. Combined treatment of BV and cisplatin induced an additive and/or weak synergistic effect towards tested cell lines, suggesting that BV could enhance the killing effect of selected cells when combined with cisplatin. Therefore, a greater anticancer effect could be triggered if BV was used in the course of chemotherapy. Our results suggest that combined treatment with BV could be useful from the point of minimizing the cisplatin concentration during chemotherapy, consequently reducing and/or postponing the development of cisplatin resistance. Copyright © 2013 John Wiley & Sons, Ltd.
    Journal of Applied Toxicology 12/2014; 34(12). DOI:10.1002/jat.2959 · 2.98 Impact Factor
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    • "Numerous studies have also reported that a component of whole HBV has several beneficial therapeutic properties, such as immune-stimulating (Son et al., 2007), anticancer (Oršolí c, 2012) and radioprotective (Gajski et al., 2009) activities. HBV contains at least 18 active components , including enzymes, biogenic amines, and several biologically active peptides, including melittin (Oršolí c, 2012). Melittin, the principal component extracted from the water-soluble fraction of HBV, is a well-recognized antibacterial peptide which acts rapidly and has a broad spectrum of activity against infectious agents including bacteria, fungi, viruses and parasites (Mataraci and Dosler, 2012; Liu et al., 2013). "
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    ABSTRACT: Honeybee (Apis melifera) venom (HBV), which includes melittin and lipid-soluble ingredients (chrysin and pinocembrin), elicited increases in the CD4(+)/CD8(+) T lymphocyte ratio, relative mRNA expression levels of the T helper type 1 (Th 1) cytokines (interferon-γ and IL-12) and reinforced viral clearance of an experimental porcine reproductive and respiratory syndrome (PRRS) virus infection in our previous study. On the basis of that previous study, we have now developed poly-d,l-lactide-co-glycolide (PLGA)-encapsulated HBV nanoparticles (P-HBV) for longer sustained release of HBV. We administered P-HBV to pigs via the rectal route, and then evaluated the potential immune-enhancing and bacterial clearance effects of P-HBV against Salmonella enterica serovar Typhimurium. The CD4(+)/CD8(+) lymphocyte ratio, proliferative capacity of peripheral blood lymphocytes and relative mRNA expression levels of IFN-γ and IL-12 (produced mainly by Th1 lymphocytes) were significantly increased in the P-HBV group up to 2 weeks post-administration of P-HBV. After S. Typhimurium infection, the P-HBV group showed a marked reduction in microbial burden in feces and all tissue samples (including the ileum, cecum, colon, and mesenteric lymph node (MLN)), a significant increase in Th 1 cytokines (IFN-γ, IL-2, and IL-12) and a marked decrease in a Th 2 cytokine (IL-4) in all tissue samples and peripheral blood lymphocytes. Thus, P-HBV may be a promising strategy for immune enhancement and prevention of S. Typhimurium or other bacterial infections.
    Veterinary Immunology and Immunopathology 08/2014; 161(3-4). DOI:10.1016/j.vetimm.2014.08.010 · 1.54 Impact Factor
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    • "Upon binding, melittin induces cytolysis of most membranes such as those of normal mammalian cells. Thus, melittin is cytotoxic in vivo which has hindered its therapeutic development, despite the fact that it inhibits or kills a range of cancer cell types, such as melanoma, osteosarcoma, leukemic, ovarian, prostate, hepatic, renal, bladder, and mammary gland cells [42]. "
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    ABSTRACT: Except for honey as food, and silk for clothing and pollination of plants, people give little thought to the benefits of insects in their lives. This overview briefly describes significant recent advances in developing insect natural products as potential new medicinal drugs. This is an exciting and rapidly expanding new field since insects are hugely variable and have utilised an enormous range of natural products to survive environmental perturbations for 100s of millions of years. There is thus a treasure chest of untapped resources waiting to be discovered. Insects products, such as silk and honey, have already been utilised for thousands of years, and extracts of insects have been produced for use in Folk Medicine around the world, but only with the development of modern molecular and biochemical techniques has it become feasible to manipulate and bioengineer insect natural products into modern medicines. Utilising knowledge gleaned from Insect Folk Medicines, this review describes modern research into bioengineering honey and venom from bees, silk, cantharidin, antimicrobial peptides, and maggot secretions and anticoagulants from blood-sucking insects into medicines. Problems and solutions encountered in these endeavours are described and indicate that the future is bright for new insect derived pharmaceuticals treatments and medicines.
    Evidence-based Complementary and Alternative Medicine 05/2014; 2014(2):904958. DOI:10.1155/2014/904958 · 1.88 Impact Factor
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