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Medical Oncology (Northwood, London,... Apr 2021Chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurological complication of cancer treatment which involves sensory and motor nerve dysfunction.... (Review)
Review
Chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurological complication of cancer treatment which involves sensory and motor nerve dysfunction. Severe CIPN has been reported in around 5% of patients treated with single and up to 38% of patients treated with multiple chemotherapeutic agents. Present medications available for CIPN are the use of opioids, nonsteroidal anti-inflammatory agents, and tricyclic antidepressants, which are only marginally effective in treating neuropathic symptoms. In reality, symptom reappears after these drugs are discontinued. The pathogenesis of CIPN has not been sufficiently recognized and methods for the prevention and treatment of CIPN remain vulnerable to therapeutic problems. It has witnessed that the present medicines available for the disease offer only symptomatic relief for the short term and have severe adverse side effects. There is no standard treatment protocol for preventing, reducing, and treating CIPN. Therefore, there is a need to develop curative therapy that can be used to treat this complication. Melittin is the main pharmacological active constituent of honeybee venom and has therapeutic values including in chemotherapeutic-induced peripheral neuropathy. It has been shown that melittin and whole honey bee venom are effective in treating paclitaxel and oxaliplatin-induced peripheral neuropathy. The use of melittin against peripheral neuropathy caused by chemotherapy has been limited despite having strong therapeutic efficacy against the disease. Melittin mediated haemolysis is the key reason to restrict its use. In our study, it is found that α-Crystallin (an eye lens protein) is capable of inhibiting melittin-induced haemolysis which gives hope of using an appropriate combination of melittin and α-Crystallin in the treatment of CIPN. The review summarizes the efforts made by different research groups to address the concern with melittin in the treatment of chemotherapeutic-induced neuropathy. It also focuses on the possible approaches to overcome melittin-induced haemolysis.
Topics: Animals; Antineoplastic Agents; Bee Venoms; Humans; Immunologic Factors; Melitten; Peripheral Nervous System Diseases
PubMed: 33796975
DOI: 10.1007/s12032-021-01496-9 -
Toxins Apr 2015While knowledge of the composition and mode of action of bee and wasp venoms dates back 50 years, the therapeutic value of these toxins remains relatively unexploded.... (Review)
Review
While knowledge of the composition and mode of action of bee and wasp venoms dates back 50 years, the therapeutic value of these toxins remains relatively unexploded. The properties of these venoms are now being studied with the aim to design and develop new therapeutic drugs. Far from evaluating the extensive number of monographs, journals and books related to bee and wasp venoms and the therapeutic effect of these toxins in numerous diseases, the following review focuses on the three most characterized peptides, namely melittin, apamin, and mastoparan. Here, we update information related to these compounds from the perspective of applied science and discuss their potential therapeutic and biotechnological applications in biomedicine.
Topics: Animals; Apamin; Humans; Intercellular Signaling Peptides and Proteins; Melitten; Peptides; Wasp Venoms
PubMed: 25835385
DOI: 10.3390/toxins7041126 -
Frontiers in Immunology 2024Melittin, a main component of bee venom, is a cationic amphiphilic peptide with a linear α-helix structure. It has been reported that melittin can exert pharmacological... (Review)
Review
Melittin, a main component of bee venom, is a cationic amphiphilic peptide with a linear α-helix structure. It has been reported that melittin can exert pharmacological effects, such as antitumor, antiviral and anti-inflammatory effects and . In particular, melittin may be beneficial for the treatment of diseases for which no specific clinical therapeutic agents exist. Melittin can effectively enhance the therapeutic properties of some first-line drugs. Elucidating the mechanism underlying melittin-mediated biological function can provide valuable insights for the application of melittin in disease intervention. However, in melittin, the positively charged amino acids enables it to directly punching holes in cell membranes. The hemolysis in red cells and the cytotoxicity triggered by melittin limit its applications. Melittin-based nanomodification, immuno-conjugation, structural regulation and gene technology strategies have been demonstrated to enhance the specificity, reduce the cytotoxicity and limit the off-target cytolysis of melittin, which suggests the potential of melittin to be used clinically. This article summarizes research progress on antiviral, antitumor and anti-inflammatory properties of melittin, and discusses the strategies of melittin-modification for its future potential clinical applications in preventing drug resistance, enhancing the selectivity to target cells and alleviating cytotoxic effects to normal cells.
Topics: Melitten; Antimicrobial Peptides; Bee Venoms; Anti-Inflammatory Agents; Antiviral Agents
PubMed: 38318188
DOI: 10.3389/fimmu.2024.1326033 -
Molecular Pharmaceutics Jul 2017Host defense peptides (HDPs) are a class of evolutionarily conserved substances of the innate immune response that have been identified as major players in the defense...
Host defense peptides (HDPs) are a class of evolutionarily conserved substances of the innate immune response that have been identified as major players in the defense system in many living organisms. Some of the HDPs are also referred to as peptidotoxins, which offer immense potential for anticancer therapy. However, their therapeutic potential is yet to be fully translated mainly due to their off-target toxicity. Here we show that their nanoenabled delivery may become beneficial in controlling their delivery in intracellular space. We introduced an amphiphilic polymer to synthesize a well-defined, self-assembled, rigid-cored polymeric nanoarchitecture for controlled delivery of three model peptidotoxins, i.e., melittin, TSAP-1, and a negative control peptide of synthetic origin. Interestingly, our results revealed strong interaction of peptidotoxins with duplex plasmid DNA. Extensive biophysical characterization (UV-vis spectroscopy, gel electrophoresis, MTT assay, and flow assisted cell sorting) experimentally verified that peptidotoxins were able to interact with genomic DNA in vitro and in turn influence the cancer cell growth. Thus, we unraveled that, through genomic DNA regulation, peptidotoxins can play a role in cell cycle regulation and exert their anticancer activities.
Topics: DNA; Melitten; Nanomedicine; Nanoparticles; Plasmids; Polymers
PubMed: 28544846
DOI: 10.1021/acs.molpharmaceut.7b00083 -
Structure and functions of channel-forming peptides: magainins, cecropins, melittin and alamethicin.The Journal of Membrane Biology Apr 1997
Comparative Study Review
Topics: Alamethicin; Amino Acid Sequence; Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Cell Membrane Permeability; Energy Metabolism; Insect Proteins; Ion Channels; Lipid Bilayers; Magainins; Melitten; Membrane Potentials; Molecular Sequence Data; Peptides; Sheep; Structure-Activity Relationship; Xenopus Proteins
PubMed: 9096062
DOI: 10.1007/s002329900201 -
Molecular and Cellular Endocrinology Apr 2007In a series of in vivo and in vitro experiments, it was shown that membrane disrupting lytic peptides (Hecate, Phor14, or Phor21) conjugated to a 15 amino acid segment... (Review)
Review
In a series of in vivo and in vitro experiments, it was shown that membrane disrupting lytic peptides (Hecate, Phor14, or Phor21) conjugated to a 15 amino acid segment of the beta chain of CG or to LHRH were able to target and destroy hormone dependent and independent human prostate cancer xenografts in nude mice. In vitro sensitivity of the cells to the drugs was directly related to LH/CG receptor expression, and pretreatment in vitro or in vivo with estrogens or FSH to enhance LH/CG receptor expression capacity and increased sensitivity to the drugs. Administration of unconjugated Hecate and LHRH was ineffective. Most importantly, all of the lytic peptide-betaCG conjugates tested were highly effective in destroying prostate cancer metastatic cells in lymph nodes, bones and lungs.
Topics: Animals; Carcinoma; Cell Survival; Chorionic Gonadotropin, beta Subunit, Human; Gonadotropin-Releasing Hormone; Humans; Male; Melitten; Necrosis; Neoplasm Metastasis; Prostatic Neoplasms
PubMed: 17382461
DOI: 10.1016/j.mce.2006.06.017 -
The Journal of Physical Chemistry. B Aug 2022We investigated d-amino acids as potential inhibitors targeting l-peptide toxins. Among the l- and d-amino acids tested, we found that d-tryptophan (d-Trp) acted as an...
We investigated d-amino acids as potential inhibitors targeting l-peptide toxins. Among the l- and d-amino acids tested, we found that d-tryptophan (d-Trp) acted as an inhibitor of melittin-induced hemolysis. We then evaluated various Trp derivatives and found that 5-chlorotryptamine (5CT) had the largest inhibitory effect on melittin. The indole ring, amino group, and steric hindrance of an inhibitor played important roles in the inhibition of melittin activity. Despite the small size and simple molecular structure of 5CT, its IC was approximately 13 μg/mL. Fluorescence quenching, circular dichroism measurements, and size-exclusion chromatography revealed that 5CT interacted with Trp19 in melittin and affected the formation of the melittin tetramer involved in hemolysis. Molecular dynamics simulation of melittin also indicated that the interaction of 5CT with Trp19 in melittin affected the formation of the tetramer.
Topics: Circular Dichroism; Hemolysis; Humans; Indoles; Melitten; Tryptophan
PubMed: 35913127
DOI: 10.1021/acs.jpcb.2c03595 -
ACS Applied Materials & Interfaces Feb 2022In this research, real-time monitoring of lipid membrane disruption is made possible by exploiting the dynamic properties of model lipid bilayers formed at oil-water...
In this research, real-time monitoring of lipid membrane disruption is made possible by exploiting the dynamic properties of model lipid bilayers formed at oil-water interfaces. This involves tracking an electrical signal generated through rhythmic membrane perturbation translated into the adsorption and penetration of charged species within the membrane. Importantly, this allows for the detection of membrane surface interactions that occur prior to pore formation that may be otherwise undetected. The requisite dynamic membranes for this approach are made possible through the droplet interface bilayer (DIB) technique. Membranes are formed at the interface of lipid monolayer-coated aqueous droplets submerged in oil. We present how cyclically alternating the membrane area leads to the generation of mechanoelectric current. This current is negligible without a transmembrane voltage until a composition mismatch between the membrane monolayers is produced, such as a one-sided accumulation of disruptive agents. The generated mechanoelectric current is then eliminated when an applied electric field compensates for this asymmetry, enabling measurement of the transmembrane potential offset. Tracking the compensating voltage with respect to time then reveals the gradual accumulation of disruptive agents prior to membrane permeabilization. The innovation of this work is emphasized in its ability to continuously track membrane surface activity, highlighting the initial interaction steps of membrane disruption. In this paper, we begin by validating our proposed approach against measurements taken for fixed composition membranes using standard electrophysiological techniques. Next, we investigate surfactant adsorption, including hexadecyltrimethylammonium bromide (CTAB, cationic) and sodium decyl sulfate (SDS, anionic), demonstrating the ability to track adsorption prior to disruption. Finally, we investigate the penetration of lipid membranes by melittin, confirming that the peptide insertion and disruption mechanics are, in part, modulated by membrane composition.
Topics: Cetrimonium; Electric Capacitance; Electrophysiology; Lipid Bilayers; Melitten; Permeability; Phosphatidylcholines; Sodium Dodecyl Sulfate; Static Electricity; Surface-Active Agents
PubMed: 35073482
DOI: 10.1021/acsami.1c19880 -
Molecules (Basel, Switzerland) May 2016Inflammation is a pervasive phenomenon triggered by the innate and adaptive immune systems to maintain homeostasis. The phenomenon normally leads to recovery from... (Review)
Review
Inflammation is a pervasive phenomenon triggered by the innate and adaptive immune systems to maintain homeostasis. The phenomenon normally leads to recovery from infection and healing, but when not properly phased, inflammation may cause immune disorders. Bee venom is a toxin that bees use for their protection from enemies. However, for centuries it has been used in the Orient as an anti-inflammatory medicine for the treatment of chronic inflammatory diseases. Bee venom and its major component, melittin, are potential means of reducing excessive immune responses and provide new alternatives for the control of inflammatory diseases. Recent experimental studies show that the biological functions of melittin could be applied for therapeutic use in vitro and in vivo. Reports verifying the therapeutic effects of melittin are accumulating in the literature, but the cellular mechanism(s) of the anti-inflammatory effects of melittin are not fully elucidated. In the present study, we review the current knowledge on the therapeutic effects of melittin and its detailed mechanisms of action against several inflammatory diseases including skin inflammation, neuroinflammation, atherosclerosis, arthritis and liver inflammation, its adverse effects as well as future prospects regarding the use of melittin.
Topics: Animals; Anti-Inflammatory Agents; Bee Venoms; Humans; Melitten
PubMed: 27187328
DOI: 10.3390/molecules21050616 -
Bioconjugate Chemistry Sep 2018Melittin (MLT), as a natural active biomolecule, can penetrate the tumor cell membrane to play a role in cancer treatment and will attract more attention in future...
Melittin (MLT), as a natural active biomolecule, can penetrate the tumor cell membrane to play a role in cancer treatment and will attract more attention in future development of antitumor drugs. The main component of natural bee venom MLT was modified by introducing a pH-sensitive amide bond between the 2,3-dimethyl maleimide (DMMA) and the lysine (Lys) of MLT (MLT-DMMA). MLT and its corresponding modified peptide MLT-DMMA were used for antitumor and biocompatibility validation. The biomaterial characteristics were tested by MALDI-TOF MS, H NMR, IUPAC and HPLC, cell viability, hemolytic and animal experiment safety evaluation. Compared with the primary melittin, the modified peptide showed decreased surface charge and low cytotoxicity in physiological conditions. Moreover, cell assays confirmed the acid-activated conversion of amide bond resulting in adequate safety during delivery and timely antitumor activity in tumor lesions. Thus, MLT-DMMA provided a feasible platform to improve the targeted and safe antitumor applications.
Topics: Acids; Animals; Antineoplastic Agents; Biocompatible Materials; Cell Survival; Chromatography, High Pressure Liquid; Drug Delivery Systems; HeLa Cells; Hemolysis; Humans; Hydrogen-Ion Concentration; Larva; Maleic Anhydrides; Melitten; Neoplasms; Proton Magnetic Resonance Spectroscopy; Reproducibility of Results; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Zebrafish
PubMed: 30148623
DOI: 10.1021/acs.bioconjchem.8b00352