“ Interestingly in our research, we found that a specif ic concentration of honeybee venom can induce 100% breast cancer cell death, while having minimal ef fects on normal cells. ”
venom and melittin rapidly killed triple-negative breast cancer and HER2-enriched breast cancer cells. Melittin in honeybee venom also had another remarkable effect. Within minutes, melittin was able to substantially reduce the chemical messages of cancer cells that are essential to cancer cell growth and cell division. We found that 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. Considering melittin forms pores in breast cancer cell membranes, we assessed whether melittin could be used with existing chemotherapy drugs, 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 breast tumour growth in mice. One of the problems that is often seen with cancer therapies is that compounds that kill cancer cells also kill healthy cells. Did you experience the same issue with the active ingredient in honeybee venom and did you do anything to target the active compound to cancer cells? Many chemotherapy drugs used clinically today are often associated with awful side effects that can reduce the quality of life of patients. Interestingly in our research, we found that a specific concentration of honeybee venom can induce 100% breast cancer cell death, while having minimal effects on normal cells. We also further enhanced the specificity of melittin by attaching a protein sequence, RGD1, to target proteins overexpressed on the membrane of triple-negative breast cancer cells, and found that this peptide ‘RGD1-melittin’ was even more selective than melittin in targeting these aggressive breast cancers.
Your research compared honeybee venom collected from populations in Western Australia, Ireland and England. Why are Perth honeybees some of the healthiest in the world – what makes them so special? Honeybees as well as other insects are dramatically declining on a global scale, a phenomenon sometimes referred to as Insectageddon. Declines in bee health are triggered by multiple factors and interactions between them including parasites, pesticide exposure, environmental changes, as well as inferior bee keeping practices. We are very lucky in Perth to have some of the healthiest honeybees in the world, and the main reason for this is due to our isolation. Bees in Western Australia are not exposed to pesticides at the same levels as elsewhere, are primarily kept in pristine and natural environments rather than in intensified agricultural landscapes, and a number of diseases that have devastated bee populations elsewhere have not yet made landfall in Western Australia. This is why it is so important not to bring bees, honey, or other bee products into Western Australia, and I hope we can continue to protect our beautiful honeybees and native bees!
Had you had much exposure to intellectual property considerations before this research and what did you learn about IP along the way? I had learned about patents and intellectual property considerations through my courses at The Centre for Entrepreneurial Research and Innovation, and Perth Biodesign, but I had never worked on a patent before protecting our research. I now understand how important the use of language is to craft a patent and specific claims to protect your intellectual property. Identifying potentially useful compounds for treating cancer is the first step – what would be the next steps for this research to translate into clinical outcomes? The next steps would involve studies to formally assess the optimum method of delivery of melittin to breast cancer cells, as well as toxicities and maximum tolerated doses. Melittin could also be combined with other drugs to find the most effective combination for different breast cancer subtypes, and also other types of cancer.
BINDHU HOLAVANAHALLI Associate
About the Harry Perkins Institute of Medical Research | www.perkins.org.au The Harry Perkins Institute of Medical Research is one Australia’s leading medical research institutes investigating diseases affecting the community. With over 250 researchers located on three hospital campuses in Perth, the Perkins is uniquely positioned to fast track the development of new discoveries and treatments. Its wholly owned clinical trials facility, Linear Clinical Research, provides international and local pharmaceutical and biotechnology companies the facilities to trial latest drugs and treatments in healthy volunteers and patients. The Harry Perkins Institute of Medical Research is proudly West Australian, providing career opportunities to our best and brightest graduates and bringing to the State international scientists. As a registered charity, the Harry Perkins Institute relies on grants and donations to fund its medical research.