Anti-Tumor Effects of Melittin and Its Potential Applications in Clinic

Lyu, Can; Fang, Fanfu; Bai, Li

doi:10.2174/1389203719666180612084615

Cited by 47 publications

(37 citation statements)

References 118 publications

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“…The anti-leukemic effects of melittin can follow different paths such as membrane disruption, energy metabolism modulation, inhibition of cell proliferation and cell death (apoptosis and necrosis) inducing [50]. One of the first studies demonstrating melittin's cytotoxic action on tumour cells was performed in 1985, Hait et al [15].…”

Section: Discussionmentioning

confidence: 99%

Melittin—A Natural Peptide from Bee Venom Which Induces Apoptosis in Human Leukaemia Cells

et al. 2020

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Bee venom is a very complex mixture produced and secreted by the honeybee (Apis mellifera). Melittin is a major component of bee venom that accounts for about 52% of its dry mass. A vast number of studies have been dedicated to the effects of melittin’s regulation of apoptosis and to the factors that induce apoptosis in various types of cancer such as breast, ovarian, prostate, lung. The latest evidence indicates its potential as a therapeutic agent in the treatment of leukaemia. The aim of our present study is to evaluate melittin’s ability to induce apoptosis in leukaemia cell lines of different origin acute lymphoblastic leukaemia (CCRF-CEM) and chronic myelogenous leukaemia (K-562). We demonstrated that melittin strongly reduced cell viability in both leukaemia cell lines but not in physiological peripheral blood mononuclear cells (PMBCs). Subsequent estimated parameters (mitochondrial membrane potential, Annexin V binding and Caspases 3/7 activity) clearly demonstrated that melittin induced apoptosis in leukaemia cells. This is a very important step for research into the development of new potential anti-leukaemia as well as anticancer therapies. Further analyses on the molecular level have been also planned (analysis of proapoptotic genes expression and DNA damages) for our next research project, which will also focus on melittin.

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Section: Discussionmentioning

confidence: 99%

Melittin—A Natural Peptide from Bee Venom Which Induces Apoptosis in Human Leukaemia Cells

et al. 2020

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“…Accumulated evidence shows that BV has anti-inflammatory, anti-apoptotic, antifibrotic, and anti-atherosclerotic properties which support these therapeutic applications [10]. In addition, a number of recent studies have demonstrated antibacterial, antiviral, antifungal, and anticancer effects of BV [1,11,12,13,14,15,16,17].…”

Section: Introductionmentioning

confidence: 99%

Potential Therapeutic Applications of Bee Venom on Skin Disease and Its Mechanisms: A Literature Review

Kim

Park

Lee

2019

Toxins

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Skin is larger than any other organ in humans. Like other organs, various bacterial, viral, and inflammatory diseases, as well as cancer, affect the skin. Skin diseases like acne, atopic dermatitis, and psoriasis often reduce the quality of life seriously. Therefore, effective treatment of skin disorders is important despite them not being life-threatening. Conventional medicines for skin diseases include corticosteroids and antimicrobial drugs, which are effective in treating many inflammatory and infectious skin diseases; however, there are growing concerns about the side effects of these therapies, especially during long-term use in relapsing or intractable diseases. Hence, many researchers are trying to develop alternative treatments, especially from natural sources, to resolve these limitations. Bee venom (BV) is an attractive candidate because many experimental and clinical reports show that BV exhibits anti-inflammatory, anti-apoptotic, anti-fibrotic, antibacterial, antiviral, antifungal, and anticancer effects. Here, we review the therapeutic applications of BV in skin diseases, including acne, alopecia, atopic dermatitis, melanoma, morphea, photoaging, psoriasis, wounds, wrinkles, and vitiligo. Moreover, we explore the therapeutic mechanisms of BV in the treatment of skin diseases and cytotoxic effects of BV on skin disease-causing pathogens, including bacteria, fungi and viruses.

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“…In summary, short peptidic natural venoms such as gomesin, melittin and the synthetic cytotoxic peptide CLIP71 can be engineered to constitute self‐assembling building blocks of tumor‐targeted nanoparticles, thus expanding the spectrum of therapeutic utilities of venoms and related peptides. Gaining nanostructure is expected to enhance the intrinsically antitumoral properties of these peptides [ 28 ] and generically, the effectiveness of any drug intended for targeted delivery. [ 29,30 ] This is because the nanoscale size allows the material fully exploiting the EPR effect, while it also prevents renal filtration.…”

Section: Figurementioning

confidence: 99%

Engineering Protein Venoms as Self‐Assembling CXCR4‐Targeted Cytotoxic Nanoparticles

Serna

Cano‐Garrido

Sánchez‐García

et al. 2020

Part & Part Syst Charact

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as self-assembling at the nanoscale, cell targeting and fluorescent emission, which might be useful for imaging purposes. This can be achieved by the construction of modular proteins that combine protein segments from different origins and with different biological activities. [3] Among such functions, the oligomerization within nanoscale dimensions and the multivalent display of cell surface peptidic ligands [4] are highly desirable to favor the enhanced retention and permeability (EPR) effect and a proper tumor biodistribution, and to estimulate the intracellular delivery in target tissues through cooperative cell binding. The incorporation of C-terminal polyhistidine peptides to modular proteins represents a simple strategy to promote robust self-assembling, as divalent metal and non-metal cations in the media, acting as molecular cross-linkers, induce protein clustering [5] and regular oligomerization in form of stable nanoparticles. [6,7] An N-terminal cationic region in the building blocks is also required for oligomerization. [6,7] Among cytotoxic proteins, venoms developed for animal predation and defense are particularly appealing as cytotoxic drugs, [8,9,10] and the possibility to engineer venoms as Protein venoms are effective cytotoxic molecules that when conveniently targeted to tumoral markers can be exploited as promising anticancer drugs. Here, it is explored whether the structurally unrelated melittin, gomesin, and CLIP71 could be functionally active when engineered, in form of GFP fusions, as self-assembling multimeric nanoparticles. Incorporated in modular constructs including a C-terminal polyhistidine tag and an N-terminal peptidic ligand of the cytokine receptor CXCR4 (overexpressed in more than 20 human neoplasias), these venoms are well produced in recombinant bacteria as proteolytically stable regular nanoparticles ranging between 12 and 35 nm. Being highly fluorescent, these materials selectively penetrate, label, and kill CXCR4 + tumor cells in a CXCR4-dependent fashion. The obtained data support the concept of recombinant venoms as promising drugs, through the precise formulation as tumor-targeted nanomaterials for selective theragnostic applications in CXCR4 + cancers.

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Anti-Tumor Effects of Melittin and Its Potential Applications in Clinic

Cited by 47 publications

References 118 publications

Melittin—A Natural Peptide from Bee Venom Which Induces Apoptosis in Human Leukaemia Cells

Melittin—A Natural Peptide from Bee Venom Which Induces Apoptosis in Human Leukaemia Cells

Potential Therapeutic Applications of Bee Venom on Skin Disease and Its Mechanisms: A Literature Review

Engineering Protein Venoms as Self‐Assembling CXCR4‐Targeted Cytotoxic Nanoparticles

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