An active component of honeybee venom rapidly killed two particularly aggressive forms of breast cancer in a laboratory study.
- New laboratory studies by a team of scientists found that the active component of honeybee venom induced death in two forms of malignant breast cancer cells that are notoriously difficult to treat.
- The magic healing molecule in the honeybees' venom appears to be melittin, which rapidly killed cancer cells in under an hour.
- In the future, doctors could potentially use melittin alongside chemotherapy drugs to increase the efficacy of the treatment.
The magic molecule<p>Previously, honeybee venom has shown potential in treating other medical conditions such as <a href="https://www.sciencealert.com/mellitin-bee-venom-eczema-inflammation-treatment" target="_blank" rel="noopener noreferrer">eczema</a> and tumors, and it has been known to <a href="https://www.sciencedirect.com/science/article/abs/pii/S0041010108003796?via%3Dihub" target="_blank" rel="noopener noreferrer">have anticancer properties</a>. How the venom works against tumors on a molecular level hasn't been understood, but science just got a lot closer. </p><p>It seems that the magic healing ingredient in the honeybees' venom is melittin — the zingy molecule responsible for producing the painful sting of a bee. Scientists at the Harry Perkins Institute of Medical Research in Perth, Australia and the University of Western Australia found that the melittin induced cancer cell death. </p><p>Their lab study, reported in the journal <a href="https://www.nature.com/articles/s41698-020-00129-0" target="_blank" rel="noopener noreferrer">NPJ Precision Oncology</a>, is the first to have looked into the effect the ingredient has on a range of breast cancers, the most common cancer in women worldwide. The two most aggressive and hard-to-treat types are known as triple-negative breast cancer (TNBC) and HER2-enriched breast cancer, which tend to mutate to resist existing treatments. The researchers found that melittin rapidly kills these cancer types and, critically, does so with no negative effects on normal cells. </p><p>"The venom was extremely potent," <a href="https://www.perkins.org.au/honeybee-venom-kills-breast-cancer-cells/" target="_blank" rel="noopener noreferrer">said</a> research leader Ciara Duffy from The Harry Perkins Institute of Medical Research in a news release. "We found that melittin can completely destroy cancer cell membranes within 60 minutes."</p><p>The lab study also found that bumblebee venom (which does not contain melittin) did not kill those particular breast cancer cells.</p>
How it works<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="df37e6f56c59da163c4ed2df27444ee7"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/K3oMN1a_pdg?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>Melittin disarms cancer cells by puncturing holes in their outer membrane. Another stunning effect: within just 20 minutes of exposure to melittin, the chemical messages cancer cells need to grow and divide are disrupted.</p><p>"We looked at how honeybee venom and melittin affect the cancer signaling pathways, the chemical messages that are fundamental for cancer cell growth and reproduction, and we found that very quickly these signaling pathways were shut down," <a href="https://www.perkins.org.au/honeybee-venom-kills-breast-cancer-cells/" target="_blank" rel="noopener noreferrer">said Duffy</a>.</p><p>The molecule is able to do this by stopping the activation of receptors that signal growth factors in the cells' membranes. The large number of these receptors in HER2-enriched cancer cells and some TNBC cells is one reason for their uncontrollable growth. Melittin seems to halt the cell's proliferation by blocking those growth signals from getting through. </p><p>"Significantly, this study demonstrates how melittin interferes with signalling pathways within breast cancer cells to reduce cell replication," said Western Australia's Chief Scientist Professor Peter Klinken. "It provides another wonderful example of where compounds in nature can be used to treat human diseases."</p>
Enhancing current cancer treatments<p>The team also tested to see if melittin could be used with existing chemotherapy drugs, as the pores in the membranes that it creates may allow other treatments to faster penetrate and kill cancer cells. </p><p>They tested the idea on a lab mouse with triple-negative breast cancer. They injected it with a combination of melittin and docetaxel — a drug used to treat a number of cancers including breast cancer. The mixture proved to be more effective at shrinking the tumors than either melittin or docetaxel alone. </p><p>In the future, doctors could potentially use melittin alongside chemotherapy drugs to enhance the efficacy of the treatment. This may allow them to reduce the dosage of chemotherapy drugs, and the adverse side effects that come with it. </p><p>The authors in the study point out that honeybee venom is inexpensive and easy to obtain, thus making it a fantastic option for cancer treatment in regions and countries with poorly resourced health services and care.</p><p>"Honeybee venom is available globally and offers cost effective and easily accessible treatment options in remote or less developed regions," <a href="https://www.nature.com/articles/s41698-020-00129-0" target="_blank" rel="noopener noreferrer">the authors write.</a> "Further research will be required to assess whether the venom of some genotypes of bees has more potent or specific anticancer activities, which could then be exploited."</p><p>Though exciting, this research is still in early, lab testing stages. The researchers will still need to perform clinical trials to assess the safety and efficacy of melittin for treating breast cancer in humans.</p>
The possibility of an easy, non-invasive detection method arises.
- A blood test that spots breast cancer five years ahead of clinical signs could give new meaning to "early detection."
- Auto-antibodies for tumor antigens predict the presence of the disease.
- Researchers say the blood test could be clinic-ready in 4-5 years.
Antigens and their auto-antibodies<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA2NzI5My9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY1Mzc1NjAxNX0.O_QXpaeuqVBb3Bp7mRWZ3pEDMTSUXC-dpYyzwW8kf4o/img.jpg?width=980" id="37f1a" class="rm-shortcode" data-rm-shortcode-id="e83fdbc7ca3c6d30dcbe71908450911e" data-rm-shortcode-name="rebelmouse-image" />
Antigens and T-cells
Image source: Juan Gaertner /Shutterstock<p>Antigens are substances produced by cells, including tumor cells. When an antigen comes into contact with other cells in the body, the immune system generates an antibody optimized specifically for that antigen called "auto-antibodies."</p><p>The team from Nottingham has found that the presence of tumor-associated antigens (TAAs) constitutes a reliable indicator of cancer. Likewise, the presence of an antigen's auto-antibody is a good indicator that the antigen, and thus a tumor, is present.</p><p>The researchers developed blood panels against which blood can be screened using <a href="https://en.wikipedia.org/wiki/Protein_microarray" target="_blank">protein microarray</a> for auto-antibodies linked to TAAs associated with breast cancer tumors. The team was able to screen for 40 such antibodies overall, as well as 27 not associated with the disease, with each panel targeted to a subset of those.</p>
The experiments<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA2NzI5OC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0NTk1NzIxN30.QvbNDA6OkknIbx5npw_qsaFNu9ez0By8XhmmhzuwYQI/img.jpg?width=980" id="661c2" class="rm-shortcode" data-rm-shortcode-id="295426b9fa3714354ddb4216d3ebe26e" data-rm-shortcode-name="rebelmouse-image" />
Image source: Victor Moussa/Shutterstock<p>The researchers from the <a href="https://www.nottingham.ac.uk/ceac/home.aspx" target="_blank">Centre of Excellence for Autoimmunity in Cancer </a>(CEAC) group at Nottingham's School of Medicine took blood samples from 90 breast cancer patients shortly after diagnosis, and from a control group of 90 volunteers not afflicted with the disease.</p><p><a href="https://www.sciencedaily.com/releases/2019/11/191103125418.htm" target="_blank">According to</a> Daniyah Alfattani, one of the researchers, "The results of our study showed that breast cancer does induce auto-antibodies against panels of specific tumor-associated antigens. We were able to detect cancer with reasonable accuracy by identifying these autoantibodies in the blood."</p><p>The team focused on three panels: One with five TAAs, one with seven, and one with nine. The larger the panel, the more accurate the testing, as it turned out.</p> <ul> <li>With the panel of five TAAs, breast cancer was detected in 29% of the samples from cancer patients, while 84% of the control samples were positively identified as being without cancer.</li> <li>With seven TAAs, the cancer-detection rate rose to 35%, while the findings of no disease in the control group went down slightly to 79%.</li> <li>A nine-TAA panel was similar, correctly detecting cancer in 37% of cancer patients, and its absence verified it in 79% of the control group. </li> </ul>
Moving forward<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA2NzMxMy9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYxNjg0MjYxMn0.dgE6sVv_1zAROrc9HtV-4sO-jVeWVVZT2Zfkk99b2pI/img.jpg?width=980" id="3154c" class="rm-shortcode" data-rm-shortcode-id="dc96f7365d50b86217ab0b9b93dfb4c7" data-rm-shortcode-name="rebelmouse-image" />
Image source: Simon Annable/Shutterstock<p>While accurate cancer detection in roughly 30% of patients isn't anywhere near good enough for widespread use as a diagnostic tool, the researchers are nonetheless upbeat about the results. "We need to develop and further validate this test," says Alfattani. "However, these results are encouraging and indicate that it's possible to detect a signal for early breast cancer. Once we have improved the accuracy of the test, then it opens the possibility of using a simple blood test to improve early detection of the disease."</p><p>Further study is currently underway with 800 patients being tested using a panel of nine TAAs, and the researchers expect to see greater accuracy in this larger cohort.</p><p>If there's a chance of substantially improving accuracy in this approach to early detection, the benefits would be obvious. Says Alfattani, "A blood test for early breast cancer detection would be cost effective, which would be of particular value in low- and middle-income countries. It would also be an easier screening method to implement compared to current methods, such as mammography."</p><p>The researchers estimate that with full funding, a clinic-ready version of the test could be developed in four to five years.</p><p>The study was presented at the <a href="https://conference.ncri.org.uk" target="_blank">2019 NCRI Cancer Conference</a> in Glasgow, and NCRI CEO Iain Frame is impressed. "Early diagnosis using simple, non-invasive ways of detecting the first signs of cancer is a key strategic priority for NCRI and something we'd all like to see working in practice. The results from this pilot study for a blood test to detect early breast cancer are promising and build on this research group's expertise in other cancers, such as lung cancer. It's obviously early days but we look forward to seeing the results from the larger group of patients that are now being investigated."</p>