Honeybee venom kills aggressive breast cancer cells

Venom from honeybees has been found to induce cancer cell death in hard-to-treat triple-negative breast cancer, with minimal effect on healthy cells. The discovey was made by Dr Ciara Duffy as part of her PhD and has been published in the journal Nature Precision Oncology.

Dr Duffy wanted to investigate the anticancer properties of honeybee venom and a component compound, melittin, on different types of breast cancer cells — including triple-negative breast cancer, which has limited treatment options. Overseen by Associate Professor Pilar Blancafort at the Harry Perkins Institute of Medical Research, and with the assistance of 312 honeybees and bumblebees, she quickly got to work.

Dr Duffy began by collecting Perth honeybee venom, with the knowledge that Perth bees are some of the healthiest in the world. She would go on to compare the effects of the venom to that of other honeybee populations in Ireland and England, as well as to bumblebees.

“The bees were put to sleep with carbon dioxide and kept on ice before the venom barb was pulled out from the abdomen of the bee and the venom extracted by careful dissection,” Dr Duffy said.

“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,” she said.

“We [also] 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 anticancer effects of honeybee venom.

“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.”

Dr Duffy described the honeybee venom as “extremely potent”, with a specific concentration of the venom found to induce 100% cancer cell death while having minimal effects on normal cells.

“I found that the European honeybee in Australia, Ireland and England produced almost identical effects in breast cancer compared to normal cells,” Dr Duffy said. “However, bumblebee venom was unable to induce cell death even at very high concentrations.”

Meanwhile, melittin was found to completely destroy cancer cell membranes within 60 minutes. The compound also had another remarkable effect — within 20 minutes, it 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,” Dr Duffy said.

“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.”

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.”

Dr 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.

“We found that melittin can be used with small molecules or chemotherapies, such as docetaxel, to treat highly aggressive types of breast cancer,” she said. “The combination of melittin and docetaxel was extremely efficient in reducing tumour growth in mice.”

In the future, studies will be required to formally assess the optimum method of delivery of melittin, as well as toxicities and maximum tolerated doses.

Image credit: ©stock.adobe.com/au/Tiangong

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