How honeybee venom destroys aggressive breast cancer cells

*New biomaterials from spider silk prevents infection, facilitates healing

Using the venom from 312 honeybees and bumblebees in Perth Western Australia, Ireland and England, Dr. Ciara Duffy from the Harry Perkins Institute of Medical Research and The University of Western Australia, tested the effect of the venom on the clinical subtypes of breast cancer, including triple-negative breast cancer, which has limited treatment options.

Results published in the prestigious international journal npj Precision Oncology revealed that honeybee venom rapidly destroyed triple-negative breast cancer and HER2-enriched breast cancer cells.

Duffy said the aim of the research was to investigate the anti-cancer properties of honeybee venom, and a component compound, melittin, on different types of breast cancer cells.

No one had previously compared the effects of honeybee venom or melittin across all of the different subtypes of breast cancer and normal cells. We tested honeybee venom on normal breast cells, and cells from the clinical subtypes of breast cancer: hormone receptor positive, HER2-enriched, and triple-negative breast cancer.

“We tested a very small, positively charged peptide in honeybee venom called melittin, which we could reproduce synthetically, and found that the synthetic product mirrored the majority of the anti-cancer effects of honeybee venom,” Duffy said.

“We found both honeybee venom and melittin significantly, selectively and rapidly reduced the viability of triple-negative breast cancer and HER2-enriched breast cancer cells. The venom was extremely potent,” Duffy said.A specific concentration of honeybee venom can induce 100 per cent cancer cell death, while having minimal effects on normal cells.

“We found that melittin can completely destroy cancer cell membranes within 60 minutes.”Melittin in honeybee venom also had another remarkable effect; within 20 minutes, melittin was able to substantially reduce the chemical messages of cancer cells that are essential to cancer cell growth and cell division.

“We looked at how honeybee venom and melittin affect the cancer signalling pathways, the chemical messages that are fundamental for cancer cell growth and reproduction, and we found that very quickly these signalling pathways were shut down.

“Melittin modulated the signalling in breast cancer cells by suppressing the activation of the receptor that is commonly overexpressed in triple-negative breast cancer, the epidermal growth factor receptor, and it suppressed the activation of HER2 which is over-expressed in HER2-enriched breast cancer,” she said.

Western Australia’s Chief Scientist Professor Peter Klinken said “This is an incredibly exciting observation that melittin, a major component of honeybee venom, can suppress the growth of deadly breast cancer cells, particularly triple-negative breast cancer.

“Significantly, this study demonstrates how melittin interferes with signalling pathways within breast cancer cells to reduce cell replication. It provides another wonderful example of where compounds in nature can be used to treat human diseases”, he said.

Duffy also tested to see if melittin could be used with existing chemotherapy drugs as it forms pores, or holes, in breast cancer cell membranes, potentially enabling the entry of other treatments into the cancer cell to enhance cell death.

One of the first reports of the effects of bee venom was published in Nature in 1950, where the venom reduced the growth of tumours in plants. However, Duffy said it was only in the past two decades that interest grew substantially into the effects of honeybee venom on different cancers.

Meanwhile, new biomaterials developed at the University of Bayreuth may eliminate the risk of infection and facilitate healing processes. A research team led by Prof. Thomas Scheibel has succeeded in combining these material properties, which are highly relevant to biomedicine. These nanostructured materials are based on spider silk proteins. They prevent colonization by bacteria and fungi, but at the same time proactively assist in the regeneration of human tissue. They are therefore ideal for implants, wound dressings, prostheses, contact lenses, and other everyday aids. The scientists have presented their innovation in the journal Materials Today.

It is a widely underestimated risk of infection: Microbes settling on the surfaces of objects indispensable in medical therapy or for quality of life generally. Gradually, they form a dense, often invisible biofilm that cannot be easily removed, even by cleaning agents, and which often is resistant against antibiotics and antimycotics. Bacteria and fungi can then migrate into the adjacent tissue of the organism. As a result, they not only interfere with various processes of healing, but also can even cause life-threatening infections.

With a novel research approach, University of Bayreuth scientists have now found a solution to this problem. Using biotechnologically produced spider silk proteins, they have developed a material that prevents the adhesion of pathogenic microbes. Even streptococci, resistant to multiple antibacterial agents (MRSA), have no chance of settling on the material surface. Biofilms growing on medical instruments, sports equipment, contact lenses, prostheses, and other everyday objects may therefore soon be history.

Moreover, the materials are designed to simultaneously aid the adhesion and proliferation of human cells on their surface. If they can be used for e.g. wound dressings, skin replacement, or implants, they proactively support the regeneration of damaged or lost tissue. In contrast to other materials that have previously been used to regenerate tissue, the risk of infection is intrinsically eliminated. Microbial-resistant coatings for a variety of biomedical and technical applications are thus set to become available in the near future.

The Bayreuth researchers have so far successfully tested the microbe-repellent function on two types of spider silk materials: on films and coatings that are only a few nanometres thick and on three-dimensional hydrogel scaffolds which can serve as precursors for tissue regeneration. “Our investigations to date have led to a finding that is absolutely ground-breaking for future research work. In particular, the microbe-repellent properties of the biomaterials we have developed are not based on toxic, i.e. not cell-destroying, effects. The decisive factor rather lies in structures at the nanometre level, which make the spider silk surfaces microbe-repellent. They make it impossible for pathogens to attach themselves to these surfaces,” explains Prof. Dr. Thomas Scheibel, who is the Chair of Biomaterials at the University of Bayreuth.

“Another fascinating aspect is that nature has once again proven to be the ideal role model for highly advanced material concepts. Natural spider silk is highly resistant to microbial infestation and the reproduction of these properties in a biotechnological way is a break-through,” adds Prof. Gregor Lang, one of the two first authors and head of the research group of Biopolymer Processing at the University of Bayreuth.

In the Bayreuth laboratories, spider silk proteins were specifically designed with various nanostructures in order to optimize biomedically relevant properties for specific applications. Once again, the networked research facilities on the Bayreuth campus have proven their worth. Together with the Bavarian Polymer Institute (BPI), three other interdisciplinary research institutes of the University of Bayreuth were involved in this research breakthrough: the Bayreuth Centre for Material Science & Engineering (BayMAT), the Bayreuth Centre for Colloids & Interfaces (BZKG), and the Bayreuth Centre for Molecular Biosciences (BZKG).