Using bees to cure cancer
Australian scientist Ciara Duffy from the University of Western Australia and the Harry Perkins Institute in Perth has discovered that the major component of honeybee venom - a molecule called “melittin” - can selectively kill cancer cells, and it looks particularly useful for targeting aggressive forms of breast cancer, including those referred to as “triple negative” tumours, that we currently struggle to treat. Chris Smith spoke to Ciara about this new work, published in npj Precision Oncology...
Ciara - For thousands of years, humans have looked at the products from bees for medicinal purposes: the honey, propolis, and the venom. And in recent years, there's been a lot of interest in terms of the venom's effects in cancer. So it's been shown to be able to kill cancer cells, but no one had actually tested that on all of the types of breast cancer and compared that to normal cells. So the way this project actually started was a veterinarian from Chile presented their research at a conference, and they'd taken these dogs, which had tumours on their sides, and they'd got these honeybees and stung into these tumours and they were shrinking and going away. And everybody in the audience went well, how does that work? Some researchers at the Perkins came together and I came in wanting to find a new treatment for breast cancer. And they said, well, we have a project looking at bees.
Chris - Where did you get the venom?
Ciara - I collected the venom from hives at the University of Western Australia, as well as at universities in London and Dublin in order to compare the venom from honey bees in different populations.
Chris - You better tell us how you actually get the venom out of a bee before you tell us what you did.
Ciara - Basically, I would take the bees by their wings or legs and put them in a box and then take them up to the lab and put them to sleep with carbon dioxide. And then very carefully under a microscope, dissect out the venom glands.
Chris - How much venom do you get per bee?
Ciara - Oh it's really tiny. It's like three microlitres. But what I do is actually dilute that because it's so potent.
Chris - What is actually in venom?
Ciara - Yeah. So it's a range of different chemicals and the main chemical is called melittin. And basically it is what has this main anticancer effect.
Chris - Right so you collect the venom, what do you then do with it?
Ciara - So I had grown up a range of cell lines in the lab representative of the different types of breast cancer, as well as normal cells. And basically diluted out the venom and tested on these cells to see if there was a difference in the effects.
Chris - And this is as simple as you just apply the venom in the liquid in which the cells are growing and see what it does to them?
Ciara - Yeah. So in terms of the cell survival, that's those experiments. And we also did microscopy to visualise actually what happened to the cells. And we can see that very quickly, the venom was able to burst open these cells and cause them to die. And remarkably the venom was more effective in these aggressive cell lines compared to the normal cells. So there was an interesting therapeutic window to play with there.
Chris - Do you know how the venom is selecting for the cancer cells, why they are particularly vulnerable, and not the healthy tissue?
Ciara - Well, there's some theories about this chemical melittin in the venom and it being more able to affect the surfaces of cancer cells because they're more vulnerable to such a chemical integrating into them. But in our research, we found that these molecules that are overexpressed or kind of more abundant in cancer cells are being shut down, and they're fundamental for the growth and replication and survival of cancer cells. So by melittin interfering with these, we think this drives some of the selectivity for damaging these cancer cells more than the normal ones.
Chris - And when melittin binds to a cancer cell, if you watch it down the microscope, what does it actually do to the cell?
Ciara - So what it does is actually 6-8 melittin molecules will come into the surface of the cell and dive in and basically form these pores or holes that cross the membrane of the cell and make the cells burst and die.
Chris - So if you've got something that makes holes in the membranes of cells, specifically cancer cells, does this mean then that even if it didn't kill the cell, you could use this almost as an adjunct therapy? You could mix it up with other drugs that sometimes struggle to get into cancer cells that are good at killing them. And then you can have a perfect cocktail of something that makes holes in cells and something that wants to get in and kill the cell?
Ciara - Yes, absolutely. And that's what we did. So we combined the compound melittin with a chemotherapy that's used for breast cancer treatment called docetaxel. And we found that the combination both in cells, but also in tumors that we had grown in mice, was significantly more potent than either melittin or docetaxel alone in reducing tumour growth and the proliferation of these tumours.
Chris - Taking this a step further then, because obviously this is early stage experiments, a lot of this work's just done looking at cells in the dish, so is the next stage then to consider how you might use this clinically?
Ciara - Yeah. So of course there's lots more experiments to do, but in terms of these aggressive and hard to treat cancers, one of the worst prognoses is for patients with triple negative breast cancer. And this one basically doesn't have any clinically effective targeted therapy. So what we hope is that we could start to develop a targeted treatment with melittin for these difficult to treat cells.