While many of us have experienced painful encounters with the pointy end of a honeybee, their weapons could be more than just a nuisance. A new lab study shows that a molecule found in bee venom can suppress the growth of particularly nasty cancer cells.
The study focussed on certain subtypes of breast cancer, including triple-negative breast cancer (TNBC), which is an extremely aggressive condition with limited treatment options.
TNBC accounts for up to 15 percent of all breast cancers. In many cases, its cells produce more of a molecule called EGFR than seen in normal cells. Previous attempts to develop treatments that specifically target this molecule have not worked, because they would also negatively affect healthy cells.
Honeybee (Apis mellifera) venom has shown potential in other medical therapies such as treating eczema, and has been known to have anti-tumour properties for some time now, including melanoma. But how it works against tumours at a molecular level isn't fully understood. Now, we've taken a huge step closer to the answer.
Bees actually use melittin - the molecule that makes up half of their venom and makes their stings really hecking painful - to fight off their own pathogens. The insects produce this peptide not just in their venom, but in other tissues too, where it's expressed in response to infections.
With their sights on this powerful molecule, researchers subjected lab-grown cancer cells and normal cells to honeybee venom from Ireland, England, and Australia, and to bumblebee (Bombus terrestris) venom from England.
They found bumblebee venom - which doesn't contain melittin, but has other potential cell-killers - had little effect on breast cancer cells, but the honeybee venom from all locations did make a difference.
"The venom was extremely potent," said medical researcher Ciara Duffy from The Harry Perkins Institute of Medical Research. "We found that melittin can completely destroy cancer cell membranes within 60 minutes."
When melittin was blocked with an antibody, the cancer cells exposed to the bee venom survived - showing that melittin was indeed the venom component responsible for the results in the earlier trials.
The best part: melittin had little impact on normal cells, specifically targeting cells that produced a lot of EGFR and HER2 (another molecule excessively produced by some breast cancer types); it even messed with the cancer cells' ability to replicate.
"This study demonstrates how melittin interferes with signalling pathways within breast cancer cells to reduce cell replication," said Western Australia's Chief Scientist Peter Klinken, who was not involved in this study.
Taking their conclusions even further, the research team also produced a synthetic version of melittin, to see how it would perform compared to the real deal.
"We found that the synthetic product mirrored the majority of the anti-cancer effects of honeybee venom," Duffy said.
Duffy and her team then tested the action of melittin paired with chemotherapy drugs in mice. The experimental treatment reduced the levels of a molecule the cancer cells use to evade detection by the immune system.
"We found that melittin can be used with small molecules or chemotherapies, such as docetaxel, to treat highly aggressive types of breast cancer," Duffy explained. "The combination of melittin and docetaxel was extremely efficient in reducing tumour growth in mice."
Over-expression of EGFR and HER2 is also seen in other types of cancers, like lung cancer, and these results suggest they might be potential targets for melittin, too.
Of course, plenty of things can kill a cancer cell in a petri dish, and the researchers caution that there's still a long way to go before this bee venom molecule could potentially be used as a treatment in humans.
"Future studies to formally assess toxicities and maximum tolerated doses of these peptides will be required prior to human trials," they wrote in their paper.
But this formidable insect weapon provides another incredible example of chemicals found in nature that could turn out to be useful for human diseases as well. However, we must remember that - like so many other creatures - honeybees are facing significant health threats of their own.
This research was published in Nature Precision Oncology.