Researchers have been interested in melittin, a peptide discovered in bee venom,
because of its possible medicinal benefits. Melittin may have actions that are
antibacterial, antiviral, anti-inflammatory, and anti-cancer, among others, according to
some data.
Here is an overview of the current scientific evidence on melittin:
Antimicrobial effects: Melittin has been demonstrated to have antibacterial effects
against a variety of gram-positive and gram-negative bacteria, including those that are
resistant to antibiotics. Bacterial cell death is hypothesised to result from the disruption of
bacterial cell membranes.
Antiviral effects: Melittin has been demonstrated in studies to have antiviral properties,
preventing the spread of viruses including hepatitis B and C, herpes simplex, and HIV.
Anti-inflammatory effects: Melittin has been demonstrated to have anti-inflammatory
properties by decreasing inflammation in animal models of different inflammatory
disorders and by inhibiting the generation of inflammatory cytokines and chemokines.
Anticancer effects: Melittin has been shown to induce apoptosis (programmed cell
death) in cancer cells and to inhibit tumor growth in animal models of various types of
cancer.
Cardiovascular effects: Melittin has been shown to have vasodilatory effects, which
could be beneficial for conditions such as hypertension and heart failure.
• Despite the fact that the data for melittin is generally positive, much more study is
required before it can be suggested as a medicinal agent.
• Because some people might experience severe allergic responses from bee venom,
any prospective use of melittin as a therapeutic should be thoroughly assessed for
safety.
More Information on Melittin:
Chemical properties: Melittin is a short peptide with 26 amino acids in it. It interacts with
negatively charged molecules like cell membranes thanks to its molecular weight of about
2.8 kDa and net positive charge.
Mode of action: Melittin exerts its biological effects by disrupting the lipid bilayer of cell
membranes. It forms pores in the membrane, which leads to the leakage of intracellular
contents and ultimately cell death. Melittin also interacts with various proteins involved in
signaling pathways and cellular processes.
Extraction and purification: Melittin alters the lipid bilayer of cell membranes in order to
produce its biological effects. It causes the membrane to develop holes, which eventually
results in cell death by allowing intracellular contents to flow out. Moreover, melittin
interacts with a number of proteins involved in cellular and signalling networks.
Potential therapeutic applications: Melittin has been investigated for its possible
therapeutic uses in a variety of conditions, including cancer, inflammation, and infectious
disorders. To evaluate melittin's effectiveness and safety in people, additional study is
nonetheless required. Also, some researchers are looking at how to alter melittin to
improve its medicinal potential or lessen its toxicity.
Safety concerns: Despite the fact that melittin has showed potential as a treatment, it's
crucial to remember that certain people may experience life-threatening allergic
responses to bee venom. High dosages of melittin can also be poisonous and have
negative consequences, including kidney damage and hemolysis (the breakdown of red
blood cells).
• Whereas melittin is an intriguing peptide with potential therapeutic uses, additional
study is required to completely comprehend its characteristics and establish its efficacy
and safety in people.
Uses of melittin in the treatment of cancer
Melittin has been investigated for its potential use in the treatment of cancer due to its
ability to induce apoptosis (programmed cell death) in cancer cells and to inhibit tumor
growth in animal models of various types of cancer.
Here are some of the ways in which melittin has been studied for its anticancer
effects:
• Induction of apoptosis: A number of cancer cells, including breast, prostate, lung,
liver, and colon cancer cells, have demonstrated the ability of melittin to trigger
apoptosis. It accomplishes this by triggering the apoptosis-promoting enzyme
caspases and interfering with mitochondrial activity..
• Inhibition of angiogenesis: It has been demonstrated that melittin prevents the
angiogenesis process, which is essential for tumour development and metastasis. It
accomplishes this by suppressing the function of the protein vascular endothelial
growth factor (VEGF), which promotes angiogenesis.
• Targeting cancer stem cells: Melittin has been shown to specifically target cancer
stem cells, a subgroup of tumour cells with the capacity to self-renew and develop into
diverse cell types. These cells are hypothesised to be the cause of treatment resistance
and tumour recurrence. Melittin has been demonstrated to prevent cancer stem cells
from self-renewing and migrating while also inducing their death.
• Synergy with other anticancer agents: When coupled with other anticancer
medications including cisplatin, doxorubicin, and paclitaxel, melittin has been proven to
have synergistic benefits. This could be because melittin makes cancer cells more
susceptible to these drugs, which increases apoptosis and slows tumour development.
Melittin is being tested in clinical studies to see how well it works when combined with
other anticancer medications to treat different forms of cancer.
How melittin is used in the treatment of cancer?
Research on the potential benefits of melittin for the treatment of cancer is still in its
infancy. There are no licenced medicines that employ melittin for the treatment of cancer
in people, despite the fact that several research have demonstrated encouraging
outcomes in animal models and in vitro trials.
As a result, scientists are looking at possible applications for melittin in the treatment of
cancer. Here are a few illustrations:
• Nanoparticle delivery: Melittin can be harmful to healthy cells at large quantities,
which makes employing it as a cancer treatment difficult. Researchers are looking at
using nanoparticles to deliver melittin directly to cancer cells while limiting harm to
healthy cells as a way to get around this problem. The efficacy of this strategy has been
demonstrated in cancer animal models, but further study is required to establish its
safety and effectiveness in people.
• Combination therapy: When used with other anticancer drugs including cisplatin,
doxorubicin, and paclitaxel, melittin has been demonstrated to have synergistic
benefits. This could be because melittin makes cancer cells more susceptible to these
drugs, which increases apoptosis and slows tumour development.
• Immunotherapy: By causing the production of cytokines, which are tiny proteins that
control the immune system, and by stimulating immune cells like macrophages and T
cells, melittin has been demonstrated to promote an immunological response against
cancer cells. As a result, melittin-based cancer immunotherapies have been created,
albeit further study is required to assess their effectiveness.
Although the fact that research on the use of melittin in the treatment of cancer is still in
its infancy, its potential for use in combination treatments or as a method of delivering
targeted nanoparticles is encouraging.
Clinical trials are now being conducted to examine its usage in conjunction with other
anticancer medications, but more study is required to determine its safety and efficacy in
people.
Evidence based articles and Links for melittin:
Melittin induces apoptosis in cancer cells:
• "Melittin suppresses growth and induces apoptosis of non-small-cell lung cancer cells
via down-regulation of TGF-β-mediated ERK signal pathway" (https://
www.ncbi.nlm.nih.gov/pmc/articles/PMC7747877/)
• "Melittin induces human gastric cancer cell apoptosis via activation of mitochondrial
pathway" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789993/)
• "Melittin, a major peptide component of bee venom, and its conjugates in cancer
therapy" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682937/
#:~:text=Melittin%20(MEL)
%2C%20a%20major,culture%20and%20animal%20model%20systems.)
Melittin inhibits angiogenesis:
• "Role of Bee Venom and Melittin on Restraining Angiogenesis and Metastasis in γ-
Irradiated Solid Ehrlich Carcinoma-Bearing Mice" (https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC7401046/)
• "Melittin, a major peptide component of bee venom, and its conjugates in cancer
therapy" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682937/)
• "Melittin suppresses cathepsin S-induced invasion and angiogenesis via blocking of
the VEGF-A/VEGFR-2/MEK1/ERK1/2 pathway in human hepatocellular
carcinoma" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727048/)
Melittin targets cancer stem cells:
• "Melittin suppresses growth and induces apoptosis of non-small-cell lung cancer cells
via down-regulation of TGF-β-mediated ERK signal pathway" (https://www.scielo.br/j/
bjmbr/a/K6VyXYGJVXHyMThRQ7yYNxy/?lang=en)
• "Melittin Induced G1 Cell Cycle Arrest and Apoptosis in Chago-K1 Human
Bronchogenic Carcinoma Cells and Inhibited the Differentiation of THP-1 Cells into
Tumour-Associated Macrophages" (https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC6428562/)
• "Dihydroartemisinin inhibits cell proliferation via AKT/GSK3β/cyclinD1 pathway and
induces apoptosis in A549 lung cancer cells" (https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC4314032/)
Melittin in combination therapy:
• "The combination of melittin and cisplatin promotes cytotoxicity and apoptosis in A549
human lung cancer cells" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682937/)
• "An Insight into the Role of Bee Venom and Melittin Against Tumor Cells: A Review of
Breast Cancer therapy" (https://www.archbreastcancer.com/index.php/abc/article/
view/374)
• "Perspectives and controversies regarding the use of natural products for the treatment
of lung cancer" (https://onlinelibrary.wiley.com/doi/10.1002/cam4.3660)
Melittin-based immunotherapy:
• "Delivery Strategies for Melittin-Based Cancer Therapy" (https://pubs.acs.org/doi/abs/
10.1021/acsami.1c03640)
• "Bee venom and melittin reduce proinflammatory mediators in lipopolysaccharide-
stimulated BV2 microglia" (https://pubmed.ncbi.nlm.nih.gov/17570326/)
• "Tumor Necrosis Factor-α Signaling in Macrophages" (https://www.ncbi.nlm.nih.gov/
pmc/articles/PMC3066460/)
Melittin and its effects on cancer cells:
• "Melittin Suppresses VEGF-A-Induced Tumor Growth by Blocking VEGFR-2 and the
COX-2-Mediated MAPK Signaling Pathway" (https://pubs.acs.org/doi/abs/10.1021/
np300446c)
• "Melittin induces apoptosis and autophagy in human cervical cancer cells" (https://
ijgc.bmj.com/content/32/Suppl_2/A6.1)
• "Melittin induces cell death and inhibits migration and invasion of ovarian cancer
cells" (https://www.sciencedirect.com/science/article/abs/pii/S0304383517303324)
Melittin and its effects on tumor growth:
• "Melittin exerts an antitumor effect on non‐small cell lung cancer cells" (https://
pubmed.ncbi.nlm.nih.gov/28713976/)
• "Honeybee venom and melittin suppress growth factor receptor activation in HER2-
enriched and triple-negative breast cancer" (https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC7463160/)
• "Therapeutic Effect of Melittin–dKLA Targeting Tumor-Associated Macrophages in
Melanoma" (https://www.researchgate.net/publication/
359215887_Therapeutic_Effect_of_Melittin-dKLA_Targeting_Tumor-
Associated_Macrophages_in_Melanoma)
Melittin and its effects on drug resistance:
• "Metabolic Reprogramming of Chemoresistant Cancer Cells and the Potential
Significance of Metabolic Regulation in the Reversal of Cancer
Chemoresistance" (https://www.mdpi.com/2218-1989/10/7/289)
• "Melittin inhibits tumor growth and decreases resistance to gemcitabine by
downregulating cholesterol pathway gene CLU in pancreatic ductal
adenocarcinoma" (https://www.sciencedirect.com/science/article/abs/pii/
S0304383517302422)
• "Natural inhibitors of PI3K/AKT signaling in breast cancer: Emphasis on newly-
discovered molecular mechanisms of action" (https://www.sciencedirect.com/science/
article/abs/pii/S104366181400190X)
Melittin-based nanomedicine:
• "Melittin-Based Nano-Delivery Systems for Cancer Therapy" (https://
www.ncbi.nlm.nih.gov/pmc/articles/PMC8773652/)
• "Delivery of melittin-loaded niosomes for breast cancer treatment: an in vitro and in
vivo evaluation of anti-cancer effect" (https://cancer-nano.biomedcentral.com/articles/
10.1186/s12645-021-00085-9)
• "Melittin-loaded polymeric nanoparticles for cancer therapy" (https://www.mdpi.com/
2218-273X/12/1/118)