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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 -
Applied Microbiology and Biotechnology Apr 2019The emergence of antibiotic-resistant bacteria, dubbed superbugs, together with relative stagnation in developing efficient antibiotics has led to enormous health and... (Review)
Review
The emergence of antibiotic-resistant bacteria, dubbed superbugs, together with relative stagnation in developing efficient antibiotics has led to enormous health and economic problems, necessitating the need for discovering and developing novel antimicrobial agents. In this respect, animal venoms represent a rich repertoire of pharmacologically active components. As a major component in the venom of European honeybee Apis mellifera, melittin has a great potential in medical applications. In this mini-review, we summarize a multitude of studies on anti-bacterial effects of melittin against planktonic and biofilm-embedded bacteria. Several investigations regarding synergistic effects between melittin and antibiotics were also described. On the whole, the properties of melittin can open up new horizons in a range of biomedical areas, from agriculture to veterinary and clinical microbiology.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bees; Biofilms; Drug Resistance, Bacterial; Drug Synergism; Melitten
PubMed: 30824944
DOI: 10.1007/s00253-019-09698-y -
ACS Applied Materials & Interfaces Apr 2021Melittin (MLT) has been studied preclinically as an anticancer agent based on its broad lytic effects in multiple tumor types. However, unsatisfactory tissue... (Review)
Review
Melittin (MLT) has been studied preclinically as an anticancer agent based on its broad lytic effects in multiple tumor types. However, unsatisfactory tissue distribution, hemolysis, rapid metabolism, and limited specificity are critical obstacles that limit the translation of MLT. Emerging drug delivery strategies hold promise for targeting, controlled drug release, reduced side effects, and ultimately improved treatment efficiency. In this review, we discuss recent advances in the use of diverse carriers to deliver MLT, with an emphasis on the design and mechanisms of action. We further outline the opportunities for MLT-based cancer immunotherapy.
Topics: Animals; Drug Delivery Systems; Humans; Melitten; Neoplasms
PubMed: 33847113
DOI: 10.1021/acsami.1c03640 -
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 -
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 -
Trends in Biochemical Sciences Nov 2014Pore-forming proteins (PFPs) interact with lipid bilayers to compromise membrane integrity. Many PFPs function by inserting a ring of oligomerized subunits into the... (Review)
Review
Pore-forming proteins (PFPs) interact with lipid bilayers to compromise membrane integrity. Many PFPs function by inserting a ring of oligomerized subunits into the bilayer to form a protein-lined hydrophilic channel. However, mounting evidence suggests that PFPs can also generate 'proteolipidic' pores by contributing to the fusion of inner and outer bilayer leaflets to form a toroidal structure. We discuss here toroidal pore formation by peptides including melittin, protegrin, and Alzheimer's Aβ1-41, as well as by PFPs from several evolutionarily unrelated families: the colicin/Bcl-2 grouping including the pro-apoptotic protein Bax, actinoporins derived from sea anemones, and the membrane attack complex-perforin/cholesterol dependent cytolysin (MACPF/CDC) set of proteins. We also explore how the structure and biological role of toroidal pores might be investigated further.
Topics: Cell Membrane; Colicins; Lipid Bilayers; Melitten; Membrane Lipids; Models, Molecular; Pore Forming Cytotoxic Proteins; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary
PubMed: 25440714
DOI: 10.1016/j.tibs.2014.09.002 -
Expert Opinion on Biological Therapy Jul 2022Melittin (MLT), a natural membrane-active component, is the most prominent cytolytic peptide from bee venom. Remarkable biological properties of MLT, including... (Review)
Review
INTRODUCTION
Melittin (MLT), a natural membrane-active component, is the most prominent cytolytic peptide from bee venom. Remarkable biological properties of MLT, including anti-inflammatory, antimicrobial, anticancer, anti-protozoan, and antiarthritic activities, make it an up-and-coming therapeutic candidate for a wide variety of human diseases. Therapeutic applications of MLT may be hindered due to low stability, high toxicity, and weak tissue penetration. Different bio-nano scale modifications hold promise for improving its functionality and therapeutic efficacy.
AREAS COVERED
In the current review, we aimed to provide a comprehensive insight into strategies used for MLT conjugations and modifications, cellular delivery of modified forms, and their clinical perspectives by reviewing the published literature on PubMed, Scopus, and Google Scholar databases. We also emphasized the MLT structure modifications, mechanism of action, and cellular toxicity.
EXPERT OPINION
Developing new analogs and conjugates of MLT as a natural drug with improved functions and fewer side effects is crucial for the clinical translation of this approach worldwide, especially where the chemicals and synthetic drugs are more expensive or unavailable in the healthcare system. MLT-nanoconjugation may be one of the best-optimized strategies for improving peptide delivery, increasing its therapeutic efficacy, and providing minimal nonspecific cellular lytic activity. [Figure: see text].
Topics: Anti-Infective Agents; Bee Venoms; Humans; Melitten; Peptides
PubMed: 35687355
DOI: 10.1080/14712598.2022.2088277 -
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 -
Environmental Toxicology and... Sep 2013Melittin (MEL) is a major peptide constituent of bee venom that has been proposed as one of the upcoming possibilities for anticancer therapy. Recent reports point to... (Review)
Review
Melittin (MEL) is a major peptide constituent of bee venom that has been proposed as one of the upcoming possibilities for anticancer therapy. Recent reports point to several mechanisms of MEL cytotoxicity in different types of cancer cells such as cell cycle alterations, effect on proliferation and/or growth inhibition, and induction of apoptotic and necrotic cell death trough several cancer cell death mechanisms, including the activation of caspases and matrix metalloproteinases. Although cytotoxic to a broad spectrum of tumour cells, the peptide is also toxic to normal cells. Therefore its therapeutic potential cannot be achieved without a proper delivery vehicle which could be overcome by MEL nanoparticles that possess the ability to safely deliver significant amount of MEL intravenously, and to target and kill tumours. This review paper summarizes the current knowledge and brings latest research findings on the anticancer potential of this lytic peptide with diverse functions.
Topics: Animals; Antineoplastic Agents; Bee Venoms; Chemistry, Pharmaceutical; Drug Carriers; Humans; Melitten; Nanoparticles
PubMed: 23892471
DOI: 10.1016/j.etap.2013.06.009 -
Journal of Cancer Research and Clinical... Dec 2023Melittin is a water-soluble cationic peptide derived from bee venom that has been thoroughly studied for the cure of different cancers. However, the unwanted... (Review)
Review
BACKGROUND
Melittin is a water-soluble cationic peptide derived from bee venom that has been thoroughly studied for the cure of different cancers. However, the unwanted interactions of melittin produce hemolytic and cytotoxic effects that hinder their therapeutic applications. To overcome the shortcomings, numerous research groups have adopted different approaches, including conjugation with tumor-targeting proteins, gene therapy, and encapsulation in nanoparticles, to reduce the non-specific cytotoxic effects and potentiate their anti-cancerous activity.
PURPOSE
This article aims to provide mechanistic insights into the chemopreventive activity of melittin and its nanoversion in combination with standard anti-cancer drugs for the treatment of cancer.
METHODS
We looked over the pertinent research on melittin's chemopreventive properties in online databases such as PubMed and Scopus.
CONCLUSION
In the present article, the anti-cancerous effects of melittin on different cancers have been discussed very nicely, as have their possible mechanisms of action to act against different tumors. Besides, it interacts with different signal molecules that regulate the diverse pathways of cancerous cells, such as cell cycle arrest, apoptosis, metastasis, angiogenesis, and inflammation. We also discussed the recent progress in the synergistic combination of melittin with standard anti-cancer drugs and a nano-formulated version of melittin for targeted delivery to improve its anticancer potential.
Topics: Animals; Melitten; Neoplasms; Antineoplastic Agents; Cell Culture Techniques; Models, Animal; Cell Proliferation
PubMed: 37919474
DOI: 10.1007/s00432-023-05458-8