Could Venom Save the Honeybee?

Could honeybee venom be used to kill aggressive cancel cells? This is the news out this month (Sept’ 2020) from research into bee venom. We all know how wonderful and important the honeybee is to our lives, but could its venom now be a key to cancer prognosis?

Honeybees are fundamental to life on Earth as the most important pollinators of food crops, however, 1/3 of the UK’s bee population has disappeared in the last decade. Despite their honey production and key responsibility in pollination, could a use in cancer treatment be their saving grace? Bee venom is a colourless, acidic liquid which bees secrete through their stingers when threatened. Recently, researchers discovered that this venom was toxic to a wide range of tumours which included melanoma, lung, ovarian and pancreatic cancers (in the lab). The active ingredient (i.e. the chemical that causes the side effect we want) of honeybee venom is melittin (a very large chemical structure which I won’t attempt to draw but that you can see HERE), and is responsible for the pain we feel when stung. However, the mode of action (i.e. how the chemical causes these effects) is still largely unknown.

On the 1st September 2020, researchers from the Harry Perkins Institute of Medical Research in Western Australia published results where bee venom had been used to target two hard-to-treat breast cancers: triple-negative and HER2-enriched (triple-negative breast cancer accounts for 15% of all breast cancers). Dr Ciara Duffy, who led the research (and is only 25 years old – why have I not achieved this already?), tested the venom from over 300 honey and bumblebees. How did they get the venom? Not from being stung thankfully. The hives were from Western Australia, London and Dublin, so the group could compare venom from different populations, and to extract the venom, Dr Duffy would put the bees in a box, put them to sleep with CO2, and then carefully extract the venom glands under a microscope, gathering tiny amounts of venom which could be diluted as it is so potent. Rather her than me…

What did the study show? Using the different cancer cell types mentioned before, Dr Duffy could compare the effects of the venom on the cancer cells with normal cells. They visualised what was happening to the cells with microscopy (i.e. a fancy way of saying they used a microscope) and, upon application of the honeybee venom, the cancer cells were bursting (and dying), whilst normal cells took a lot longer to do so. But how does honeybee venom select for the cancer cells over healthy cells? This is still not known for sure, but the researchers observed that key chemicals which are over-expressed by cancer cells were being shut down in the presence of the venom. Such chemicals are fundamental to the growth, replication and survival of the cancer cells, and thus, if the melittin in honeybee venom is interfering with these chemicals, cancer cells will be selected before healthy cells. Six to eight melittin molecules were seen to cross the cancer cell membrane (see diagram) and formed holes/pores in the cells, causing them to burst and die. However, bumblebee venom does not contain melittin and had little effect on the cancer cells.

A lot more research is needed before we see honeybee venom widely used in hospitals as a cancer treatment, what dosage will kill cancer cells but leave healthy ones unscathed, etc.? But it may not just be a stand alone treatment, many chemotherapy drugs are adjuncts (e.g. multiple drugs used together used to increase the efficacy or safety of a primary treatment), and melittin could be the same. By creating holes in the surface of cancer cells, this could open up (pun intended) the opportunity for potent cancer drugs which have previously failed to enter cancer cells to achieve their therapeutic effect. This is a problem for many drugs; they’re potent in theory but they just can’t break a cancer cell’s membrane. Again, researchers experimented with this concept, combining melittin with chemotherapy drug Docetaxel, which is used for breast cancer. Dr Duffy and the team saw that this combination was more potent than either drug when used alone, effective in both cells in the lab and tumours in mice.

Although this may not be the first time honeybee venom has been used for medicinal purposes (in fact, honeybee venom has been used for thousands of years to treat inflammation amongst other ailments), these findings from Dr Duffy and her colleagues are very exciting. I’m not sure cultivating honeybees for their venom will necessarily save them though, and whilst this could be a therapy of the future, I won’t be sticking myself in a bee hive anytime soon…

To hear more from Dr Duffy, head to The Naked Scientist podcast and give this week’s episode a listen (the bee venom section starts at 19:45), HERE.

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