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 journal npj
Precision Oncology revealed that honeybee venom rapidly
destroyed triple-negative breast cancer and HER2-enriched breast cancer cells.
Dr 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,” Dr 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,” Dr Duffy said.
A specific concentration of honeybee venom can induce
100% 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.
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. The combination of melittin and docetaxel was extremely
efficient in reducing tumour growth in mice.”
Dr Duffy’s research was conducted as part of her PhD
undertaken at Perth’s Harry Perkins Institute of Medical Research at the Cancer
Epigenetics laboratory overseen by A/Prof. Pilar Blancafort. “I began with
collecting Perth honeybee venom. Perth bees are some of the healthiest in the
world.
“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,” she said.
While there are 20,000 species of bees, Dr Duffy
wanted to compare the effects of Perth honeybee venom to other honeybee
populations in Ireland and England, as well as to the venom of bumblebees.
“I found that the European honeybee in Australia,
Ireland and England produced almost identical effects in breast cancer compared
to normal cells. However, bumblebee venom was unable to induce cell death even
at very high concentrations.
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, Dr Duffy said it was only in the past two decades that
interest grew substantially into the effects of honeybee venom on different
cancers.
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.
Source: https://www.perkins.org.au/honeybee-venom-kills-breast-cancer-cells/
Journal article: https://www.nature.com/articles/s41698-020-00129-0
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