Bee venom molecule attacks breast cancer
Researchers in Western Australia have created a buzz about how honeybee venom kills breast cancer cells...
For thousands of years, people have used beestings and honey to heal wounds and fight infections. Now cancer might be joining that list. This is because honeybee venom contains a molecule called melittin, which accounts for about half of the dry weight of the venom. It’s a small, positively-charged protein that spears cell membranes and opens up pores that electrically destabilise and kill the targeted cell in a matter of minutes.
The initial inklings of this effect were documented in the 1950s when scientists were able to show that bee venom could stunt the growth of tumours in tomato and wheat plants1. Since then, interest in the possibility of translating these effects into the animal kingdom and specifically human medicine has grown significantly, particularly as the chemical components in the venom - and their mechanisms of action in cells - have been worked out.
Consequently, scientists had gone on to show that honeybee venom can kill some types of breast cancer cells, but nobody had formally investigated the effectiveness of the venom at destroying some of the aggressive subtypes of breast cancer, or compared this to what happens when normal breast cells are exposed.
More generally, while it was known that many venoms target cancers, the underlying molecular reason for why this happens was not understood. Could bee venom be selective for specific breast cancers? And could we improve or engineer melittin to make it even more potent?
These were the questions that I set out to tackle during my PhD at the Harry Perkins Institute of Medical Research in Perth, Western Australia. Working with the team there, I've found that honeybee venom is remarkably effective in killing aggressive forms of breast cancer cells, including cells from hard-to-treat "HER2-enriched" and "triple-negative" cancers. Critically, there was minimal impact on healthy cells.
The first step was collecting sufficient amounts of bee venom. Luckily, Perth has some of the healthiest bees in the world, due to their isolation, and I used insects from hives at the University of Western Australia (UWA). To extract the venom, each of hundreds of bees were picked up gently by their wings or legs at the entrance of the hive, put to sleep with carbon dioxide, and the venom harvested by dissecting out the venom gland.
We tested the venom against 11 different cell lines representing the different clinical subtypes of breast cancer, as well as normal breast cells to see whether these would be affected. Alongside the bee venom extracts, we also tested an artificial melittin, made chemically, so we could identify whether the effects were purely down to melittin itself, or whether there were other cancer-active components present.
The results showed that honeybee venom rapidly killed breast cancer cells and at concentrations that had minimal effects on normal cells. Down the microscope, melittin in the venom got to work quickly and attacked the cancer cell membranes in just minutes. Reports have shown that honeybee venom and melittin can have higher killing potency to cancer cells compared to normal cells in specific types of cancer, which could be due to differences between the characteristics of normal and cancer cell membranes, making cancer cells more vulnerable to molecules such as melittin. In our research, signalling pathways and chemical messengers crucial for the breast cancer cells to grow were being shut down within minutes of melittin treatment.
But because melittin forms holes in cell membranes, it's possible that it might also enhance the ability of other anti-cancer drugs to get into cancer cells. To explore this, we injected melittin alongside the chemotherapy drug docetaxel into mice with triple-negative breast cancers. This combination was significantly more effective in reducing tumour growth compared to either melittin or docetaxel alone.
Meanwhile, to find out if it was just Perth's bees that are blessed with this ability, we also obtained venom from honeybees in Ireland and England, as well as other bee species including worker and queen buff-tailed bumblebees.
Reassuringly, the effect of the different honeybee venoms on breast cancer and normal cells were remarkably similar, regardless of where the insects came from. But bumblebee venom, on the other hand, barely worked at all even at very high concentrations, showing that honeybees are the anti-cancer kings, or rather queens!
Overall, these findings suggest that honeybee venom, and in particular the melittin it contains, might help us to develop better targeted treatment for breast cancers, including disease like HER2-enriched and triple-negative breast cancers that currently carry the worst prognoses.
This research was supported by an Australian Government Research Training Program (RTP) Scholarship, and a PhD Top Up Scholarship from the Cancer Council of Western Australia.