Honeybee Venom - A New Insight Towards Breast Cancer Research

 

Honeybee Venom - A New Insight Towards Breast Cancer Research

 

The venom produced from honeybees is said to have a variety of medicinal properties, which are being studied widely. One such recent study conducted by Harry Perkins Institute of Medical Research has shown that honeybee venom consists of a component which helps to combat against two aggressive types of Breast Cancer.

Breast Cancer is the most common form of cancer among women, where cancer cells are formed in breasts which impacts around 2.1 million women each year and causing a huge number of cancer-related deaths among women (nearly 15%).Henceforth it always pushes scientists all over the world to come up with more effective treatment although a variety ofprocedures are existing already.

According to the new study conducted by Harry Perkins Institute of Medical Research, it has revealed that honey bee venom possesses a property that brings about the death of Triple-negative breast cancer cells and HER-2 augmented breast cancer cells with minimal effect on healthy cells. Triple-negative breast cancer tests negative for Estrogen receptors, Progesterone receptors and excess HER-2 protein, which makes difficulty in treating by hormonal therapy and it contributes to 10-20% of breast cancers. HER-2 breast cancer cells test positive for a protein called human epidermal growth factor receptor 2(HER-2), a protein promoting growth of cancer cells.

This case study was conducted by Dr Ciara Duffy, The University of Western Australia, Perth, using the venom from 312 honey bees and bumblebees in Perth, Western Australia, Ireland and England. The objective of this research is to analyze the effect of venom on various subtypes of breast cancer and to examine anti-cancer properties of venom and its component called Melittin on breast cancer cells. It was found that these cancer cells are vulnerable to honey bee venom and melittin as they've shown remarkable effect precisely reduced the triple-negative breast cancer and HER-2 enriched breast cancer cells. These findings are published in Nature Precision Oncology.

This study has shown that melittin disrupts the cancer cell membranes and destroys them completely by apoptosis. Another astounding effect of melittin isthat it regulates the cell cycle in cancer cells by reducing their chemical messages.

Melittin

- It forms the major component (40-60%) of honeybee venom, and it is responsible for causing pain.

- It is a peptide molecule made up of 26 amino, basic.

 - In general protein structures are made of di-sulfide bridges which helps in providing stability to tertiary and quaternary forms, however, melittin lacks it.

 - Melittin molecule is made up of a hydrophobic N - terminal part and a hydrophilic C - terminal part which is basic.

 - Upon injection into living beings it causes pore formation in epithelial cells and the annihilation of red blood cells.

·       This very own mechanism forms the basis for battling the targeted cancer cells where the injected venom gets associated with the bilayer phospholipid membrane of the of malignant cells and brings about death by the formation of pores, enabling the internalization of additional nanoparticles with cytotoxic activities.

 

  Structure of Melittin

To evaluate the anti-cancer safety and efficacy they collected venom from honeybeesand also cell lines representing the intrinsic subtypes of breast cancer. Cell lines in cell culture are areasin which all the cells possess only a particular trait unique to a cell from which it is developed thereby constituting the uniform genetic makeup. These studies were carried out in Dose-Response assays where the action of venom compounds against the cell lines and non transformed cells were observed. Careful analysis showed that the honey bee venom showed high anti-cancer selectivity enough to produce ripples of impactwith higher potency is found in Triple-negative breast cancer (SUM 159 and SUM 149) and in HER-2 enriched breast cell lines ( MDA-MB-453 and SKBR3), which is followed by luminal breast cancer cells ( MCF-7 and T-47D) with the minimal effect on normal cells. In comparison with the normal HDFa cell line, it also showsa reduction in the half-maximal inhibitory concentration (IC50) for both the TNBC SUM 159 and HER-2 enriched SKBR3 cancer cell lines was noticed.

Not only with the venom of honeybees but they also studied the venom collected from the Bumblebees (Bombusterristris) from England. Where the samples were collected from both workers and queens showed a little effect in causing death when compared to honeybee’svenom even when employed it employed in remarkably high concentrations. To assess the relative abundance of melittin in all the honeybee and bumble bee venom samples they developed a mouse monoclonal antibody by ELISA. The study displayed that there was not much difference in the relative abundance of melittin among a variety of honeybee samples collected from different locations.

 

The anticancer properties of melittin were established by in vitro experiments where an anti-melittin antibody is employed to rescue cell viability in HDFa and SUM 159 cells. As already the cells are administered with an antibody that expresses against melittin, the same cells when treated with honey bee venom encounters with antibody and can't induce the apoptosis pathway hence the higher cell viability was significantly observed suggesting the role of melittin as a prominent bioactive cancer compound.  Association of melittin with the negatively charged plasma membrane is mediated by positivelycharged C-terminus induces the formation of pores and leads to cell lysis. Removal of positive charged C- terminus significantly reduces the binding capacity of melittin, compared to wild melittin.

This recent revelation has garnered much attention and paved a new direction in the field of cancer treatment using Apitherapy. Melittin, from honeybee venom, can be synthesized in-vitro using microbial transformation and can be further used as an anti-cancer drug. Furthermore, melittin coupled with other chemotherapeutic drugs helps in ceasing tumor progression. Also, melittin, when is administered with docetaxel forms (a potent formulation), showed exceptional results in controlling breast cancer progression. Further research in the field will help in safe and efficient administration of the melittin based drugs in treating breast cancers.

References:

Duffy, C., Sorolla, A., Wang, E., Golden, E., Woodward, E., Davern, K., Ho, D., Johnstone, E., Pfleger, K., Redfern, A., Iyer, K., Baer, B. and Blancafort, P., 2020. Honeybee venom and melittin suppress growth factor receptor activation in HER2-enriched and triple-negative breast cancer. npj Precision Oncology, 4(1).