Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Goran Gajski
 -- 2281 2024-03-08 09:04:22 |
2 format
Jason Zhu
 Meta information modification 2281 2024-03-12 03:27:08 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Gajski, G.; Leonova, E.; Sjakste, N. Anticancer Effects of Bee Venom and Its Components. Encyclopedia. Available online: https://encyclopedia.pub/entry/56051 (accessed on 18 May 2024).
Gajski G, Leonova E, Sjakste N. Anticancer Effects of Bee Venom and Its Components. Encyclopedia. Available at: https://encyclopedia.pub/entry/56051. Accessed May 18, 2024.
Gajski, Goran, Elina Leonova, Nikolajs Sjakste. "Anticancer Effects of Bee Venom and Its Components" Encyclopedia, https://encyclopedia.pub/entry/56051 (accessed May 18, 2024).
Gajski, G., Leonova, E., & Sjakste, N. (2024, March 08). Anticancer Effects of Bee Venom and Its Components. In Encyclopedia. https://encyclopedia.pub/entry/56051
Gajski, Goran, et al. "Anticancer Effects of Bee Venom and Its Components." Encyclopedia. Web. 08 March, 2024.
Anticancer Effects of Bee Venom and Its Components
Edit
This entry is adapted from the peer-reviewed paper 10.3390/toxins16030117

Among the various natural compounds used in alternative and Oriental medicine, toxins isolated from different organisms have had their application for many years, and Apis mellifera venom has been studied the most extensively. Numerous studies dealing with the positive assets of bee venom (BV) indicated its beneficial properties. The usage of bee products to prevent the occurrence of diseases and for their treatment is often referred to as apitherapy and is based mainly on the experience of the traditional system of medical practice in diverse ethnic communities. Today, a large number of studies are focused on the antitumor effects of BV, which are mainly attributed to its basic polypeptide melittin (MEL). 

natural products apitherapy apitoxin bee venom melittin phospholipase A2

1. Anticancer Effects of Bee Venom

Today, large numbers of studies are being conducted to explore the antitumor action of BV towards different types of cancers and the underlying mechanisms. The anticancer effect is mainly accredited to a basic polypeptide, MEL, that makes up about 50% of the dry BV. Havas [1] was one of the first who recorded the impact of BV on cancer cells. Afterward, Mufson and colleagues [2] reported that MEL can pass through a phospholipid bilayer, and thus display its ability. The relation between MEL and cell membranes caused impairment of the phospholipid’s acyl groups, higher sensitivity to phospholipid hydrolysis by phospholipase, and increased synthesis of prostaglandins from arachidonic acid released from phospholipids. Furthermore, McDonald et al. [3] examined BV’s anticancer property in a mortality study which involved 580 beekeepers. Beekeepers were identified through the obituaries published in three different US beekeeping industry journals between 1949 and 1978. Based on the obituaries, they established the cause of death of the beekeepers and made a comparison with the general population. Results showed a slightly lower incidence of death from cancer in beekeepers professionally exposed to BV during their working life compared to the rest of the population and a significantly lower death rate from lung cancer, while the mortality from other diseases was equal to the rest of the general population. The obtained results were among the first to suggest the possible anticancer potential of BV. After that, numerous studies showed anticancer properties of BV and its major component MEL [4][5][6][7][8][9][10][11][12][13][14].

2. Anticancer Effect of Melittin

Hait et al. [15] were the first to demonstrate an inhibiting potential of MEL in vitro. They showed that MEL, as an inhibitor of calmodulin, inhibits the growth and clonogenic capacity of human leukemia cells. Lee and Hait [16] have also observed an inhibitory impact of MEL on astrocytoma cell growth. Lazo et al. [17] noted a comparable mechanism of action of MEL as an inhibitor of calmodulin in leukemia cells. They also noted that MEL enhances bleomycin toxicity in human granulocyte macrophages and erythroid stem cell colonies [18]. Hait and Lee [19] noted that the cytotoxicity of MEL is proportional to the antagonistic effect of calmodulin. The aforementioned studies support the pharmacological role of calmodulin as a potential intracellular target of MEL antiproliferative activity.
Additionally, Killion and Dunn [20] showed that leukemia cells are more sensitive to MEL action compared to normal mouse spleen cells and bone marrow cells, reasoning that bone marrow cells have several binding sites on the membrane for carbohydrates, and these places disappear in the adult spleen cells, while they are almost absent after neoplastic changes that could make cancer cells more sensitive to the peptide. Zhu et al. [21] have reported that MEL does not prevent the growth of normal cells at a concentration that prevents the proliferation of cancer cells such as lung cancer cells. The observed cell response differences indicated an unalike activation of signaling pathways between normal and cancer cells. MEL has proven particularly effective in cultured cells that express high levels of the ras oncogene [22][23]. MEL also enhances the PLA2 activation in the ras oncogene-transformed cells resulting in its selective destruction. The results suggest that the enhanced activation of PLA2 by MEL could be the target of MEL’s cytotoxicity against cancer cells [5].

3. Anticancer Effects of Phospholipase A2

MEL causes increased activation of PLA2 activity and calcium intake in ras-transformed cells, which could be the basis for the antitumor activity of this compound [23]. Following these findings, a large number of studies made a connection between PLA2 activity and MEL’s cytotoxic effect on a variety of tumor cells [24][25][26][27]. Activation of PLA2 could play a role in the cytotoxicity of tumor cells through several different cell changes such as a synergistic effect of PLA2 and phosphatidylinositol (3,4)-bisphosphate in the induction of cell death [28]. Death caused by PLA2 and phosphatidylinositol (3,4)-bisphosphate is associated with the disruption of cell membrane integrity, abolition of signal transduction, and creation of a cytotoxic lyso-phosphatidylinositol (3,4)-bisphosphate. It was also found that their combined effect results in the formation of a tumor lysate that enhances the maturation of human monocyte-derived immunostimulatory dendritic cells. Such a tumor lysate, which is a complex mixture of tumor antigens with potential activity, has everything needed for a potential tumor vaccine [29].

4. The Mechanisms of Bee Venom and Melittin Anticancer Activity

One of the main issues in anticancer therapy is related to the concentration of the substance used, as it may cause serious side effects. Therefore, drug intake should be adequate and specific. A large number of insect lithic peptides, including those isolated from BV, have an amphipathic structure that binds and incorporates into negatively charged cell membranes. Compared to normal cells, which have a low membrane potential, the membrane of cancer cells has a high membrane potential [5][6][30][31] and that is why numerous lytic peptides selectively disrupt the membrane structure of cancer cells rather than the normal cell membrane. MEL should thus have a suitable role in anticancer therapy [5]. Gawronska et al. [32] have thus found that MEL is toxic to ovarian cancer cells and that the toxicity is dose-dependent.
Bee venom-induced apoptosis has been observed both in vitro and in vivo. Liu et al. [33] observed that BV inhibits the proliferation of melanoma cancer cells both in vitro and in vivo. The apoptosis observed in those cells was regarded as one of the possible mechanisms of action by which BV inhibits proliferation and induces differentiation of those same cells in vitro. Apoptosis was also observed in lung cancer cells by inhibition of cyclooxygenase 2 (COX-2) [34] and in osteosarcoma cells by increased Fas expression after BV treatment [35]. Holle et al. [31] observed that the MEL avidin conjugate has strong cytolytic activity in cells with a high metalloproteinase activity, such as prostate and ovary cancer cells. In contrast, the same activity was much lower in normal cells with limited metalloproteinase activity in vitro. In vivo, a significant reduction in tumor size was observed after treatment with the MEL avidin conjugate compared to untreated tumors. These studies also suggest the possible application of MEL avidin conjugate for therapeutic purposes. Moon et al. [30] suggested a molecular mechanism by which BV causes apoptosis in leukemia. Apoptosis was induced by reduced regulation of ERK and Akt signaling pathway. Furthermore, apoptosis induced by BV was associated with the downregulation of Bcl-2, caspase-3 activation, and cleavage of poly (ADP-ribose) polymerase (PARP). Moreover, induction of apoptosis was accompanied by a reduced regulation of inhibitory apoptosis protein (IAP proteins). BV also activated p38, MAPK, and JNK and decreased regulation of ERK and Akt [5].
These results indicate that the induction of apoptosis might have a role in the anticancer activity of BV and MEL, although the mechanisms behind this induction have still not been fully elucidated. Moreover, the apoptosis induction in cancer cells is also shown throughout gene therapy with MEL [36]. As the possibility of using the peptides from BV in anticancer therapy has been attracting increasing attention in recent years, Hu et al. [37] also found that these peptides could successfully kill liver cancer cells both in vitro and in vivo. A major mechanism of cancer growth inhibition by these peptides is again cell death induced by apoptosis. Oršolić et al. [38] have found that intravenous application of BV significantly reduces the number of lung metastases in mice. However, subcutaneous BV intake failed to show such a good effect on metastases, indicating route dependence as well as the proximity effects of BV when used for anticancer purposes.
Previous studies indicated that BV and MEL can induce strong toxic effects in various cancer cells such as lung, liver, kidney, breast, prostate, bladder, and leukemic cells, with a less pronounced effect in normal cells [5][6][7]. The proposed mechanisms of action are mainly related to the activation of PLA2, caspase, and matrix metalloproteinases that destroy cancer cells [30][31]. Conjugation of MEL with hormone receptors and MEL gene therapy could be useful in the future treatment of breast and prostate cancer [36][39][40][41]. Accordingly, MEL as an amphipathic protein may have a desirable role in therapeutic purposes. MEL is particularly active against cultured cells that express high levels of the ras oncogene [22][23]. Additionally, MEL enhances PLA2 activity in the ras oncogene-transformed cells, which results in their selective destruction, suggesting that such hyperactivation of PLA2 by MEL could be one of the major pathways of MEL’s cytotoxic activity against cancer cells [5].
In the past few decades, numerous studies showed quite potent anticancer effects of BV and MEL towards various cancer cells such as hepatocellular cells, prostate cells, lung cells, bladder cells, ovarian cells, mammary cells, and melanocyte cells, as well as in leukemia through different mechanisms of action [5][7][9][42].
The numerous cellular effects of BV and MEL summarized above need explanation on a molecular level, and the main issue here has to do with the trigger of the apoptotic cascade. Apoptosis could be either a consequence of the plasmatic membrane fenestration or the result of the direct interaction of BV components with pro-apoptotic and anti-apoptotic factors. Interaction of BV peptides and enzymes with the plasma membrane is a crucial step in the whole process.
Application of biophysical methods showed that MEL brought a small decrease in local membrane fluidity in homogeneous lipid membranes, as the lipids appear to be more closely packed in the proximity of the MEL pore. On the contrary, in heterogeneous lipid membranes in cells, the local order of lipids is diminished by the peptide [43]. The selective affinity of MEL to cancer cells is determined mostly by acidic phosphatidylserine exposure to the outer layer of the cell membrane in cancer cells [44]. The binding of MEL to the membranes causes the formation of non-bilayer lipid phases in the membranes [45]. According to data from computer modeling, after penetration, the lipid bilayer MEL can adopt either a transmembrane or a U-shaped conformation. Several peptides of different conformations aggregate to form a pore. In the pores, peptides are organized in a manner such that polar residues face inward and hydrophobic residues face outward, which stabilizes the pores and forms water channels [46]. Depending on the local concentration of MEL, it can induce toroidal pores owing to the collective insertion of multiple MEL peptides from the N-termini. The pore formation is initiated by a local increase in membrane curvature in the vicinity of the peptide aggregate. Pore formation can be also achieved by a detergent-like mechanism when lipids are extracted or bursting, causing rapid formation of a large pore in a strongly curved membrane [47]. Membrane cholesterol impedes pore formation by MEL [48]. Membrane deformities induced by MEL enhance the activity of PLA2, and the synergistic action of the two BV components enhances the lytic effect of the venom [49].
Besides membrane lipids, MEL can directly interact with plasma membrane proteins, Na/K ATPase, for example. Binding causes inhibition of the enzyme [50]. MEL stimulates TRPM2 Ca2+ channels in glioblastoma cells, decreasing their resistance to chemotherapy [51]. BV and MEL suppress the activation of EGFR and HER2 in triple-negative and HER2-enriched breast cancer cells by interfering with the phosphorylation of these receptors in the plasma membrane [52]. Reports about the suppression of the Wnt/β-catenin pathway by MEL suggest the destruction of the Wnt receptors by the peptide [53].
What happens after the formation of the pore? Sure, it enables an influx of free radicals which can damage the cell; however, it seems that MEL action is better targeted. It was shown that MEL directly affected the mitochondrial membrane of the human lung adenocarcinoma cells A549. MEL caused changes in mitochondrial membrane potential, triggered mitochondrial ROS burst, and activated the mitochondria-related apoptosis pathway Bax/Bcl-2 [54]. Interaction with the mitochondrial membrane is localized to the cardiolipin-rich sites, where non-bilayer structures are formed [55]. Indeed, this effect is already sufficient to induce the terminal stage of apoptosis—leakage of cytochrome C, formation of apoptosomes, activation of executioner caspases, and fragmentation of chromatin.
MEL can also interact with proteins involved in different regulation pathways. MEL and calmodulin complexes can even be crystallized [56] and used as a model system of protein–protein complexes. Multiple binding modes exist. Whereas the helical structure of MEL remains, the swapping of its salt bridges and partial unfolding of its C-terminal segment can occur. Different sets of residues can anchor at the hydrophobic pockets of calmodulin, which are considered the main recognition sites [57]. A block of calmodulin can cause disruptions of the PI3K/Akt and other pathways caused by BV; numerous data have been summarized in recent exhaustive reports [42][58].
Being a positively charged peptide, MEL can directly interact with DNA and RNA [59][60]. Data about these interactions are few and might indicate direct damage of DNA by MEL or interference in the transcription mechanism. Treatment with BV triggers the intensive accumulation of the γ-H2AX histone, a marker of the DNA double-strand breaks, in cancer cell nuclei, but the effect is not observed in normal fibroblasts [61]. MEL binds centrin, an enzyme involved in nucleotide-excision repair. Binding is stabilized by the hydrophobic triads—leucine–leucine–tryptophan [59]. BV causes changes in the mitochondrial genome by modification of the methylation pattern and mitochondrial DNA copy number [62].

References

  1. Havas, L.J. Effect of Bee Venom on Colchicine-Induced Tumours. Nature 1950, 166, 567–568.
  2. Mufson, R.A.; Laskin, J.D.; Fisher, P.B.; Weinstein, I.B. Melittin Shares Certain Cellular Effects with Phorbol Ester Tumour Promoters. Nature 1979, 280, 72–74.
  3. McDonald, J.A.; Li, F.P.; Mehta Cyrus, R. Cancer Mortality Among Beekeepers. J. Occup. Med. 1979, 21, 811–813.
  4. Sjakste, N.; Gajski, G. A Review on Genotoxic and Genoprotective Effects of Biologically Active Compounds of Animal Origin. Toxins 2023, 15, 165.
  5. Son, D.J.; Lee, J.W.; Lee, Y.H.; Song, H.S.; Lee, C.K.; Hong, J.T. Therapeutic Application of Anti-Arthritis, Pain-Releasing, and Anti-Cancer Effects of Bee Venom and Its Constituent Compounds. Pharmacol. Ther. 2007, 115, 246–270.
  6. Gajski, G.; Garaj-Vrhovac, V. Melittin: A Lytic Peptide with Anticancer Properties. Environ. Toxicol. Pharmacol. 2013, 36, 697–705.
  7. Oršolić, N. Bee Venom in Cancer Therapy. Cancer Metast. Rev. 2012, 31, 173–194.
  8. Khalil, A.; Elesawy, B.H.; Ali, T.M.; Ahmed, O.M. Bee Venom: From Venom to Drug. Molecules 2021, 26, 4941.
  9. Ullah, A.; Aldakheel, F.M.; Anjum, S.I.; Raza, G.; Khan, S.A.; Tlak Gajger, I. Pharmacological Properties and Therapeutic Potential of Honey Bee Venom. Saudi Pharm. J. 2023, 31, 96–109.
  10. Nainu, F.; Masyita, A.; Bahar, M.A.; Raihan, M.; Prova, S.R.; Mitra, S.; Emran, T.B.; Simal-Gandara, J. Pharmaceutical Prospects of Bee Products: Special Focus on Anticancer, Antibacterial, Antiviral, and Antiparasitic Properties. Antibiotics 2021, 10, 822.
  11. Małek, A.; Strzemski, M.; Kurzepa, J.; Kurzepa, J. Can Bee Venom Be Used as Anticancer Agent in Modern Medicine? Cancers 2023, 15, 3714.
  12. Chaisakul, J.; Hodgson, W.C.; Kuruppu, S.; Prasongsook, N. Effects of Animal Venoms and Toxins on Hallmarks of Cancer. J. Cancer 2016, 7, 1571–1578.
  13. Chatterjee, B. Animal Venoms Have Potential to Treat Cancer. Curr. Top. Med. Chem. 2018, 18, 2555–2566.
  14. Liu, C.-C.; Hao, D.-J.; Zhang, Q.; An, J.; Zhao, J.-J.; Chen, B.; Zhang, L.-L.; Yang, H. Application of Bee Venom and Its Main Constituent Melittin for Cancer Treatment. Cancer Chemother. Pharmacol. 2016, 78, 1113–1130.
  15. Hait, W.N.; Grais, L.; Benz, C.; Cadman, E.C. Inhibition of Growth of Leukemic Cells by Inhibitors of Calmodulin: Phenothiazines and Melittin. Cancer Chemother. Pharmacol. 1985, 14, 202–205.
  16. Lee, G.L.; Hait, W.N. Inhibition of Growth of C6 Astrocytoma Cells by Inhibitors of Calmodulin. Life Sci. 1985, 36, 347–354.
  17. Lazo, J.S.; Hait, W.N.; Kennedy, K.A.; Braun, I.D.; Meandzija, B. Enhanced Bleomycin-Induced DNA Damage and Cytotoxicity with Calmodulin Antagonists. Mol. Pharmacol. 1985, 27, 387–393.
  18. Lazo, J.S.; Chen, D.-L.; Gallicchio, V.S.; Hait, W.N. Increased Lethality of Calmodulin Antagonists and Bleomycin to Human Bone Marrow and Bleomycin-Resistant Malignant Cells. Cancer Res. 1986, 46, 2236–2240.
  19. Hait, W.N.; Lee, G.L. Characteristics of the Cytotoxic Effects of the Phenothiazine Class of Calmodulin Antagonists. Biochem. Pharmacol. 1985, 34, 3973–3978.
  20. Killion, J.J.; Dunn, J.D. Differential Cytolysis of Murine Spleen, Bone-Marrow and Leukemia Cells by Melittin Reveals Differences in Membrane Topography. Biochem. Biophys. Res. Commun. 1986, 139, 222–227.
  21. Zhu, H.; Tayeh, I.; Israel, L.; Castagna, M. Different Susceptibility of Lung Cell Lines to Inhibitors of Tumor Promotion and Inducers of Differentiation. J. Biol. Regul. Homeost. Agents 1991, 5, 52–58.
  22. Sharma, S.V. Melittin Resistance: A Counterselection for Ras Transformation. Oncogene 1992, 7, 193–201.
  23. Sharma, S. Melittin-Induced Hyperactivation of Phospholipase A2 Activity and Calcium Influx in Ras-Transformed Cells. Oncogene 1993, 8, 939–947.
  24. Hanada, K.; Kinoshita, E.; Itoh, M.; Hirata, M.; Kajiyama, G.; Sugiyama, M. Human Pancreatic Phospholipase A2 Stimulates the Growth of Human Pancreatic Cancer Cell Line. FEBS Lett. 1995, 373, 85–87.
  25. Arora, A.S.; de Groen, P.C.; Croall, D.E.; Emori, Y.; Gores, G.J. Hepatocellular Carcinoma Cells Resist Necrosis during Anoxia by Preventing Phospholipase-Mediated Calpain Activation. J. Cell. Physiol. 1996, 167, 434–442.
  26. Wu, Y.-L.; Jiang, X.-R.; Newland, A.C.; Kelsey, S.M. Failure to Activate Cytosolic Phospholipase A2 Causes TNF Resistance in Human Leukemic Cells. J. Immunol. 1998, 160, 5929–5935.
  27. Saini, S.S.; Chopra, A.K.; Peterson, J.W. Melittin Activates Endogenous Phospholipase D during Cytolysis of Human Monocytic Leukemia Cells. Toxicon 1999, 37, 1605–1619.
  28. Putz, T.; Ramoner, R.; Gander, H.; Rahm, A.; Bartsch, G.; Thurnher, M. Antitumor Action and Immune Activation through Cooperation of Bee Venom Secretory Phospholipase A2 and Phosphatidylinositol-(3,4)-Bisphosphate. Cancer Immunol. Immunother. 2006, 55, 1374–1383.
  29. Putz, T.; Ramoner, R.; Gander, H.; Rahm, A.; Bartsch, G.; Bernardo, K.; Ramsay, S.; Thurnher, M. Bee Venom Secretory Phospholipase A2 and Phosphatidylinositol-Homologues Cooperatively Disrupt Membrane Integrity, Abrogate Signal Transduction and Inhibit Proliferation of Renal Cancer Cells. Cancer Immunol. Immunother. 2007, 56, 627–640.
  30. Moon, D.-O.; Park, S.-Y.; Heo, M.-S.; Kim, K.-C.; Park, C.; Ko, W.S.; Choi, Y.H.; Kim, G.-Y. Key Regulators in Bee Venom-Induced Apoptosis Are Bcl-2 and Caspase-3 in Human Leukemic U937 Cells through Downregulation of ERK and Akt. Int. Immunopharmacol. 2006, 6, 1796–1807.
  31. Holle, L.; Song, W.; Holle, E.; Wei, Y.; Wagner, T.; Yu, X. A Matrix Metalloproteinase 2 Cleavable Melittin/Avidin Conjugate Specifically Targets Tumor Cells In Vitro and In Vivo. Int. J. Oncol. 2003, 22, 93–98.
  32. Gawronska, B.; Leuschner, C.; Enright, F.M.; Hansel, W. Effects of a Lytic Peptide Conjugated to β HCG on Ovarian Cancer: Studies In Vitro and In Vivo. Gynecol. Oncol. 2002, 85, 45–52.
  33. Liu, X.; Chen, D.; Xie, L.; Zhang, R. Effect of Honey Bee Venom on Proliferation of K1735M2 Mouse Melanoma Cells In-Vitro and Growth of Murine B16 Melanomas in-Vivo. J. Pharm. Pharmacol. 2002, 54, 1083–1089.
  34. Jang, M.-H.; Shin, M.-C.; Lim, S.; Han, S.-M.; Park, H.-J.; Shin, I.; Lee, J.-S.; Kim, K.-A.; Kim, E.-H.; Kim, C.-J. Bee Venom Induces Apoptosis and Inhibits Expression of Cyclooxygenase-2 MRNA in Human Lung Cancer Cell Line NCI-H1299. J. Pharmacol. Sci. 2003, 91, 95–104.
  35. Chen, Y.-Q.; Zhu, Z.-A.; Hao, Y.-Q.; Dai, K.-R.; Zhang, C. Effect of Melittin on Apoptsis and Necrosis of U2OS Cells. J. Chin. Integr. Med. 2004, 2, 208–209.
  36. Li, B.; Ling, C.; Zhang, C.; Gu, W.; Li, S.; Huang, X.; Zhang, Y.; Yu, C. The Induced Apoptosis of Recombinant Adenovirus Carrying Melittin Gene for Hepatocellular Carcinoma Cell. Zhonghua Gan Zang Bing Za Zhi 2004, 12, 453–455.
  37. Hu, H.; Chen, D.; Li, Y.; Zhang, X. Effect of Polypeptides in Bee Venom on Growth Inhibition and Apoptosis Induction of the Human Hepatoma Cell Line SMMC-7721 In-Vitro and Balb/c Nude Mice in-Vivo. J. Pharm. Pharmacol. 2006, 58, 83–89.
  38. Orsolić, N.; Sver, L.; Verstovsek, S.; Terzić, S.; Basić, I. Inhibition of Mammary Carcinoma Cell Proliferation In Vitro and Tumor Growth In Vivo by Bee Venom. Toxicon 2003, 41, 861–870.
  39. Russell, P.J.; Hewish, D.; Carter, T.; Sterling-Levis, K.; Ow, K.; Hattarki, M.; Doughty, L.; Guthrie, R.; Shapira, D.; Molloy, P.L.; et al. Cytotoxic Properties of Immunoconjugates Containing Melittin-like Peptide 101 against Prostate Cancer: In Vitro and In Vivo Studies. Cancer Immunol. Immunother. 2004, 53, 411–421.
  40. Li, S.; Ling, C.; Liu, X. Impact of Infection with Recombinant Adenovirus Carrying Melittin Gene on CD54 Expression in HepG2 Cells. Di Yi Jun Yi Da Xue Xue Bao 2003, 23, 300–305.
  41. Ling, C.-Q.; Li, B.; Zhang, C.; Gu, W.; Li, S.-X.; Huang, X.-Q.; Zhang, Y.-N. Anti-Hepatocarcinoma Effect of Recombinant Adenovirus Carrying Melittin Gene. Zhonghua Gan Zang Bing Za Zhi 2004, 12, 741–744.
  42. Pandey, P.; Khan, F.; Khan, M.A.; Kumar, R.; Upadhyay, T.K. An Updated Review Summarizing the Anticancer Efficacy of Melittin from Bee Venom in Several Models of Human Cancers. Nutrients 2023, 15, 3111.
  43. Zorilă, B.; Necula, G.; Radu, M.; Bacalum, M. Melittin Induces Local Order Changes in Artificial and Biological Membranes as Revealed by Spectral Analysis of Laurdan Fluorescence. Toxins 2020, 12, 705.
  44. Li, J.; Hanlon, P.; Gasanoff, E.S. Interaction of Bee Venom Melittin, a Potential Anti-Cancer Drug, with Phosphatidylcholine Membrane Enriched with Phosphatidylserine. EC Pharmacol. Toxicol. 2020, 8, 119–129.
  45. Li, M.; Gasanoff, E.S. Cationic Proteins Rich in Lysine Residue Trigger Formation of Non-Bilayer Lipid Phases in Model and Biological Membranes: Biophysical Methods of Study. J. Membr. Biol. 2023, 256, 373–391.
  46. Sun, L.; Wang, S.; Tian, F.; Zhu, H.; Dai, L. Organizations of Melittin Peptides after Spontaneous Penetration into Cell Membranes. Biophys. J. 2022, 121, 4368–4381.
  47. Miyazaki, Y.; Shinoda, W. Cooperative Antimicrobial Action of Melittin on Lipid Membranes: A Coarse-Grained Molecular Dynamics Study. Biochim. Biophys. Acta Biomembr. 2022, 1864, 183955.
  48. Ganpule, S.; Vijaya, A.K.; Sukova, A.; Preta, G. Membrane Cholesterol Content and Lipid Organization Influence Melittin and Pneumolysin Pore-Forming Activity. Toxins 2022, 14, 346.
  49. Jepson, T.A.; Hall, S.C.; Chung, J.K. Single-Molecule Phospholipase A2 Becomes Processive on Melittin-Induced Membrane Deformations. Biophys. J. 2022, 121, 1417–1423.
  50. Shorina, E.A.; Dolgova, N.V.; Rubtsov, A.M.; Storey, K.B.; Lopina, O.D. Melittin Induces Both Time-Dependent Aggregation and Inhibition of Na,K-ATPase from Duck Salt Glands However These Two Processes Appear to Occur Independently. Biochim. Biophys. Acta 2004, 1661, 188–195.
  51. Ertilav, K.; Nazıroğlu, M. Honey Bee Venom Melittin Increases the Oxidant Activity of Cisplatin and Kills Human Glioblastoma Cells by Stimulating the TRPM2 Channel. Toxicon 2023, 222, 106993.
  52. Duffy, C.; Sorolla, A.; Wang, E.; Golden, E.; Woodward, E.; Davern, K.; Ho, D.; Johnstone, E.; Pfleger, K.; Redfern, A.; et al. Honeybee Venom and Melittin Suppress Growth Factor Receptor Activation in HER2-Enriched and Triple-Negative Breast Cancer. npj Precis. Oncol. 2020, 4, 24.
  53. Xie, X.; Li, Y.; Zhu, H.; Chen, L.; Chen, D.; Lin, S.; Fan, T. Melittin Inhibits Growth of Human Osteosarcoma 143B Cells through Induction of Apoptosis via Suppressing the Wnt/β-Catenin Signaling Pathway. Anticancer. Agents Med. Chem. 2022, 22, 3172–3181.
  54. Li, X.; Li, Z.; Meng, Y.-Q.; Qiao, H.; Zhai, K.-R.; Li, Z.-Q.; Wei, S.-L.; Li, B. Melittin Kills A549 Cells by Targeting Mitochondria and Blocking Mitophagy Flux. Redox Rep. 2023, 28, 2284517.
  55. Gasanoff, E.; Liu, Y.; Li, F.; Hanlon, P.; Garab, G. Bee Venom Melittin Disintegrates the Respiration of Mitochondria in Healthy Cells and Lymphoblasts, and Induces the Formation of Non-Bilayer Structures in Model Inner Mitochondrial Membranes. Int. J. Mol. Sci. 2021, 22, 11122.
  56. Korovesis, D.; Gaspar, V.P.; Beard, H.A.; Chen, S.; Zahédi, R.P.; Verhelst, S.H.L. Mapping Peptide–Protein Interactions by Amine-Reactive Cleavable Photoaffinity Reagents. ACS Omega 2023, 8, 25487–25495.
  57. Dürvanger, Z.; Juhász, T.; Liliom, K.; Harmat, V. Structures of Calmodulin-Melittin Complexes Show Multiple Binding Modes Lacking Classical Anchoring Interactions. J. Biol. Chem. 2023, 299, 104596.
  58. Shi, P.; Xie, S.; Yang, J.; Zhang, Y.; Han, S.; Su, S.; Yao, H. Pharmacological Effects and Mechanisms of Bee Venom and Its Main Components: Recent Progress and Perspective. Front. Pharmacol. 2022, 13, 1001553.
  59. Zhang, W.; Shi, E.; Zhao, Y.; Yang, B. Inhibitory Effect of Melittin on Endonuclease-like Activity of Centrin. J. Inorg. Biochem. 2018, 186, 280–293.
  60. Shi, W.; Li, C.; Li, M.; Zong, X.; Han, D.; Chen, Y. Antimicrobial Peptide Melittin against Xanthomonas Oryzae Pv. Oryzae, the Bacterial Leaf Blight Pathogen in Rice. Appl. Microbiol. Biotechnol. 2016, 100, 5059–5067.
  61. Tetikoğlu, S.; Çelik-Uzuner, S. Bee Venom Induces the Interaction between Phosphorylated Histone Variant, H2AX, and the Intracellular Site of Beta-Actin in Liver and Breast Cancer Cells. Chem. Biodivers. 2023, 20, e202300401.
  62. Uzuner, S.Ç.; Birinci, E.; Tetikoğlu, S.; Birinci, C.; Kolaylı, S. Distinct Epigenetic Reprogramming, Mitochondrial Patterns, Cellular Morphology, and Cytotoxicity after Bee Venom Treatment. Recent Pat. Anticancer Drug Discov. 2021, 16, 377–392.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Toxicology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Goran Gajski
,
Elina Leonova
,
Nikolajs Sjakste
View Times: 67
Revisions: 2 times (View History)
Update Date: 12 Mar 2024
Table of Contents
    1000/1000
    Hot Most Recent
    Feedback