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Biomolecules Jan 2022Melittin (MEL) is a 26-amino acid polypeptide with a variety of pharmacological and toxicological effects, which include strong surface activity on cell lipid membranes,... (Review)
Review
Melittin (MEL) is a 26-amino acid polypeptide with a variety of pharmacological and toxicological effects, which include strong surface activity on cell lipid membranes, hemolytic activity, and potential anti-tumor properties. However, the clinical application of melittin is restricted due to its severe hemolytic activity. Different nanocarrier systems have been developed to achieve stable loading, side effects shielding, and tumor-targeted delivery, such as liposomes, cationic polymers, lipodisks, etc. In addition, MEL can be modified on nano drugs as a non-selective cytolytic peptide to enhance cellular uptake and endosomal/lysosomal escape. In this review, we discuss recent advances in MEL's nano-delivery systems and MEL-modified nano drug carriers for cancer therapy.
Topics: Drug Carriers; Humans; Liposomes; Melitten; Nanoparticle Drug Delivery System; Neoplasms
PubMed: 35053266
DOI: 10.3390/biom12010118 -
Toxins Mar 2021Bee venom, which is a complex substance produced by , is widely used to treat various diseases, such as pain [...].
Bee venom, which is a complex substance produced by , is widely used to treat various diseases, such as pain [...].
Topics: Acupuncture Therapy; Animals; Apamin; Bee Venoms; Bees; Humans; Melitten; Phospholipases A2
PubMed: 33799931
DOI: 10.3390/toxins13030191 -
Toxins Feb 2024Among the various natural compounds used in alternative and Oriental medicine, toxins isolated from different organisms have had their application for many years, and... (Review)
Review
Among the various natural compounds used in alternative and Oriental medicine, toxins isolated from different organisms have had their application for many years, and 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). Previous studies have indicated that BV and its major constituent MEL cause a strong toxic effect on different cancer cells, such as liver, lung, bladder, kidney, prostate, breast, and leukemia cells, while a less pronounced effect was observed in normal non-target cells. Their proposed mechanisms of action, such as the effect on proliferation and growth inhibition, cell cycle alterations, and induction of cell death through several cancer cell death mechanisms, are associated with the activation of phospholipase A (PLA), caspases, and matrix metalloproteinases that destroy cancer cells. Numerous cellular effects of BV and MEL need to be elucidated on the molecular level, while the key issue 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 the BV components with pro-apoptotic and anti-apoptotic factors. The interaction of BV peptides and enzymes with the plasma membrane is a crucial step in the whole process. However, before its possible application as a remedy, it is crucial to identify the correct route of exposure and dosage of BV and MEL for potential therapeutic use as well as potential side effects on normal cells and tissues to avoid any possible adverse event.
Topics: Male; Animals; Bees; Bee Venoms; Melitten; Cell Membrane; Apoptosis; Cell Death
PubMed: 38535786
DOI: 10.3390/toxins16030117 -
Redox Report : Communications in Free... Dec 2024Melittin, the main component of bee venom, is a natural anti-inflammatory substance, in addition to its ability to fight cancer, antiviral, and useful in diabetes...
OBJECTIVES
Melittin, the main component of bee venom, is a natural anti-inflammatory substance, in addition to its ability to fight cancer, antiviral, and useful in diabetes treatment. This study seeks to determine whether melittin can protect renal tissue from sepsis-induced damage by preventing ferroptosis and explore the protective mechanism.
METHODS
In this study, we investigated the specific protective mechanism of melittin against sepsis-induced renal injury by screening renal injury indicators and ferroptosis -related molecules and markers in animal and cellular models of sepsis.
RESULTS
Our results showed that treatment with melittin attenuated the pathological changes in mice with lipopolysaccharide-induced acute kidney injury. Additionally, we found that melittin attenuated ferroptosis in kidney tissue by enhancing GPX4 expression, which ultimately led to the reduction of kidney tissue injury. Furthermore, we observed that melittin enhanced NRF2 nuclear translocation, which consequently upregulated GPX4 expression. our findings suggest that melittin may be a potential therapeutic agent for the treatment of sepsis-associated acute kidney injury by inhibiting ferroptosis through the GPX4/NRF2 pathway.
CONCLUSIONS
Our study reveals the protective mechanism of melittin in septic kidney injury and provides a new therapeutic direction for Sepsis-AKI.
Topics: Animals; Mice; Melitten; Ferroptosis; NF-E2-Related Factor 2; Acute Kidney Injury; Sepsis
PubMed: 38149613
DOI: 10.1080/13510002.2023.2290864 -
Journal of Nanobiotechnology Aug 2023Sentinel lymph node (SLN) metastasis is an important promoter of distant metastasis in breast cancer. Therefore, the timely diagnosis and precise treatment are crucial...
Sentinel lymph node (SLN) metastasis is an important promoter of distant metastasis in breast cancer. Therefore, the timely diagnosis and precise treatment are crucial for patient staging and prognosis. However, the simultaneous diagnosis of metastasis and the implementation of imaging-guided SLN therapy is challenging. Here, we report a melittin-loaded and hyaluronic acid (HA)-conjugated high-density lipoprotein (HDL) mimic phospholipid scaffold nanoparticle (MLT-HA-HPPS), which dually-target to both breast cancer and its SLN and efficiently inhibit SLN metastasis in the LN metastasis model. The melittin peptide was successfully loaded onto HA-HPPS via electrostatic interactions, and MLT-HA-HPPS possesses effective cytotoxicity for breast cancer 4T1 cells. Moreover, the effective delivery of MLT-HA-HPPS from the primary tumor into SLN is monitored by NIR fluorescence imaging, which greatly benefits the prognosis and treatment of metastatic SLNs. After paracancerous administration, MLT-HA-HPPS can efficiently inhibit primary tumor growth with an inhibition rate of 81.3% and 76.5% relative to the PBS-treated control group and HA-HPPS group, respectively. More importantly, MLT-HA-HPPS can effectively inhibit the growth of the metastatic SLNs with an approximately 78.0%, 79.1%, and 64.2% decrease in SLNs weight than those in PBS, HA-HPPS, and melittin-treated mice, respectively. Taken together, the MLT-HA-HPPS may provide an encouraging theranostic of SLN drug delivery strategy to inhibit primary tumor progression and prevent SLN metastasis of breast cancer.
Topics: Mice; Animals; Sentinel Lymph Node; Sentinel Lymph Node Biopsy; Melitten; Lymphatic Metastasis; Nanoparticles; Lymph Nodes
PubMed: 37528426
DOI: 10.1186/s12951-023-02026-7 -
Toxins Jul 2022While the survival rate has increased due to treatments for breast cancer, the quality of life has decreased because of the side effects of chemotherapy. Various toxins... (Review)
Review
While the survival rate has increased due to treatments for breast cancer, the quality of life has decreased because of the side effects of chemotherapy. Various toxins are being developed as alternative breast cancer treatments, and bee venom is drawing attention as one of them. We analyzed the effect of bee venom and its components on breast cancer cells and reviewed the mechanism underlying the anticancer effects of bee venom. Data up to March 2022 were searched from PubMed, EMBASE, OASIS, KISS, and Science Direct online databases, and studies that met the inclusion criteria were reviewed. Among 612 studies, 11 were selected for this research. Diverse drugs were administered, including crude bee venom, melittin, phospholipase A2, and their complexes. All drugs reduced the number of breast cancer cells in proportion to the dose and time. The mechanisms of anticancer effects included cytotoxicity, apoptosis, cell targeting, gene expression regulation, and cell lysis. Summarily, bee venom and its components exert anticancer effects on human breast cancer cells. Depending on the mechanisms of anticancer effects, side effects are expected to be reduced by using various vehicles. Bee venom and its components have the potential to prevent and treat breast cancer in the future.
Topics: Apoptosis; Bee Venoms; Breast Neoplasms; Female; Humans; Melitten; Quality of Life
PubMed: 35878198
DOI: 10.3390/toxins14070460 -
Biochemical Pharmacology Nov 2021Melittin, the main venom component of the European Honeybee, is a cationic linear peptide-amide of 26 amino acid residues with the sequence:... (Review)
Review
Melittin, the main venom component of the European Honeybee, is a cationic linear peptide-amide of 26 amino acid residues with the sequence: GIGAVLKVLTTGLPALISWIKRKRQQ-NH. Melittin binds to lipid bilayer membranes, folds into amphipathic α-helical secondary structure and disrupts the permeability barrier. Since melittin was first described, a remarkable array of activities and potential applications in biology and medicine have been described. Melittin is also a favorite model system for biophysicists to study the structure, folding and function of peptides and proteins in membranes. Melittin has also been used as a template for the evolution of new activities in membranes. Here we overview the rich history of scientific research into the many activities of melittin and outline exciting future applications.
Topics: Animals; Bees; Gene Expression Regulation; Melitten; Phylogeny; Protein Conformation
PubMed: 34543656
DOI: 10.1016/j.bcp.2021.114769 -
Neuroscience Bulletin Jun 2016Melittin is a basic 26-amino-acid polypeptide that constitutes 40-60% of dry honeybee (Apis mellifera) venom. Although much is known about its strong surface activity on... (Review)
Review
Melittin is a basic 26-amino-acid polypeptide that constitutes 40-60% of dry honeybee (Apis mellifera) venom. Although much is known about its strong surface activity on lipid membranes, less is known about its pain-producing effects in the nervous system. In this review, we provide lines of accumulating evidence to support the hypothesis that melittin is the major pain-producing substance of bee venom. At the psychophysical and behavioral levels, subcutaneous injection of melittin causes tonic pain sensation and pain-related behaviors in both humans and animals. At the cellular level, melittin activates primary nociceptor cells through direct and indirect effects. On one hand, melittin can selectively open thermal nociceptor transient receptor potential vanilloid receptor channels via phospholipase A2-lipoxygenase/cyclooxygenase metabolites, leading to depolarization of primary nociceptor cells. On the other hand, algogens and inflammatory/pro-inflammatory mediators released from the tissue matrix by melittin's pore-forming effects can activate primary nociceptor cells through both ligand-gated receptor channels and the G-protein-coupled receptor-mediated opening of transient receptor potential canonical channels. Moreover, subcutaneous melittin up-regulates Nav1.8 and Nav1.9 subunits, resulting in the enhancement of tetrodotoxin-resistant Na(+) currents and the generation of long-term action potential firing. These nociceptive responses in the periphery finally activate and sensitize the spinal dorsal horn pain-signaling neurons, resulting in spontaneous nociceptive paw flinches and pain hypersensitivity to thermal and mechanical stimuli. Taken together, it is concluded that melittin is the major pain-producing substance of bee venom, by which peripheral persistent pain and hyperalgesia (or allodynia), primary nociceptive neuronal sensitization, and CNS synaptic plasticity (or metaplasticity) can be readily induced and the molecular and cellular mechanisms underlying naturally-occurring venomous biotoxins can be experimentally unraveled.
Topics: Animals; Bee Venoms; Bees; Melitten; Nociceptors; Pain
PubMed: 26983715
DOI: 10.1007/s12264-016-0024-y -
Redox Report : Communications in Free... Dec 2023Melittin, a naturally occurring polypeptide found in bee venom, has been recognized for its potential anti-tumor effects, particularly in the context of lung cancer. Our...
Melittin, a naturally occurring polypeptide found in bee venom, has been recognized for its potential anti-tumor effects, particularly in the context of lung cancer. Our previous study focused on its impact on human lung adenocarcinoma cells A549, revealing that melittin induces intracellular reactive oxygen species (ROS) burst and oxidative damage, resulting in cell death. Considering the significant role of mitochondria in maintaining intracellular redox levels and ROS, we further examined the involvement of mitochondrial damage in melittin-induced apoptosis in lung cancer cells. Our findings demonstrated that melittin caused changes in mitochondrial membrane potential (MMP), triggered mitochondrial ROS burst (Figure 1), and activated the mitochondria-related apoptosis pathway Bax/Bcl-2 by directly targeting mitochondria in A549 cells (Figure 2). Further, we infected A549 cells using a lentivirus that can express melittin-Myc and confirmed that melittin can directly target binding to mitochondria, causing the biological effects described above (Figure 2). Notably, melittin induced mitochondrial damage while inhibiting autophagy, resulting in abnormal degradation of damaged mitochondria (Figure 5). To summarize, our study unveils that melittin targets mitochondria, causing mitochondrial damage, and inhibits the autophagy-lysosomal degradation pathway. This process triggers mitoROS burst and ultimately activates the mitochondria-associated Bax/Bcl-2 apoptotic signaling pathways in A549 cells.
Topics: Humans; Mitophagy; A549 Cells; Melitten; Reactive Oxygen Species; bcl-2-Associated X Protein; Mitochondria; Apoptosis; Membrane Potential, Mitochondrial; Lung Neoplasms
PubMed: 38041592
DOI: 10.1080/13510002.2023.2284517 -
Nutrients Jul 2023Apitherapy (using bee products) has gained broad recognition in cancer therapeutics globally. Honeybee venom has a broad range of biological potential, and its... (Review)
Review
Apitherapy (using bee products) has gained broad recognition in cancer therapeutics globally. Honeybee venom has a broad range of biological potential, and its utilization is rapidly emerging in apitherapy. Bee products have significant potential to strengthen the immune system and improve human health. Thus, this review is targeted toward recapitulating the chemo-preventive potential of melittin (MEL), which constitutes a substantial portion of honeybee venom. Honeybee venom (apitoxin) is produced in the venom gland of the honeybee abdomen, and adult bees utilize it as a primary colony defense mechanism. Apitoxin comprises numerous biologically active compounds, including peptides, enzymes, amines, amino acids, phospholipids, minerals, carbohydrates, and volatile components. We are mainly focused on exploring the potential of melittin (a peptide component) of bee venom that has shown promising potential in the treatment of several human cancers, including breast, stomach, lung, prostate, ovary, kidney, colon, gastric, esophageal, cervical cancers, melanoma, osteosarcoma, and hepatocellular carcinoma. This review has summarized all potential studies related to the anticancerous efficacy of melittin (apitoxin), its formulations, conjugates, and nano-formulations against several human carcinomas, which would further pave the way for future researchers in developing potent drugs for cancer management.
Topics: Male; Humans; Bees; Animals; Bee Venoms; Melitten; Peptides; Carcinoma, Hepatocellular; Liver Neoplasms; Bone Neoplasms
PubMed: 37513529
DOI: 10.3390/nu15143111