Anish Pyne, Indian Institute of Technology Kharagpur
Although we usually tend to fear the painful sting of a Honeybee since our early childhood days, science offers a different perspective for it. Studies suggest that honeybee venom can be one of the most crucial weapons for mankind. Recently, an in vitro study conducted in Harry Perkins Institute of Medical Research by Duffy et al. 2020 showed that a compound which is known as Melittin, present in honeybee venom successfully destroys TNBC (Triple Negative Breast Cancer) cells, which characteristically over-expresses HER-2 (Human Epidermal Receptor-2) and EGFR (Epidermal Growth Factor Receptors). The study also mentioned that Melittin showed nominal toxicity against healthy host cells, and thus is highly specific towards cancerous cells only. This crucial aspect that is occurring in this particular scenario has been the lacking factor amongst many of the well-known cancer treatment procedures (especially chemotherapies) discovered and practiced so far.
TNBC is amongst the most aggressive forms of Breast Cancers, and have a much poorer prognosis compared to the other types of Breast Cancers. Usually, the TNBC cells are characterised by their overexpression of certain cell-surface receptors (localised in the plasma membrane of breast carcinoma cells) like EGFRs and HER-2, which are capitalised by Melittin as it induces apoptosis in these cells by inhibiting phosphorylation of HER-2 and EGFR and thus blocking their activation. Mutational studies have revealed that the positively charged C-terminal of Melittin mediates this inhibition of phosphorylation.
The study focussed on the collection of honeybee venom from the species– Apis mellifera (common name: Western honey bee), which were collected from Ireland, England and Australia. Alongside, the collection of venom from bumblebees occurring in England was conducted and was set as the negative control. It was observed that the bumblebee venom which lacked Melittin had nominal cytolytic activity on TNBC cells, whereas honeybee venom from all the varying samples created a significant difference by decreasing the number of the TNBC cells.
Duffy and colleagues also managed to synthesise a synthetic form of Melittin to check whether there were any other co-stimulatory molecules in the honeybee venom that resulted in the activation of Melittin. And that then showed them that the synthetic form of Melittin mimicked the majority of the anti-cancer effects of naturally occurring Melittin from honeybee venom, giving them the conclusion that Melittin is solely responsible for inducing apoptosis of TNBC cells.
Melittin treatment also enhances the action of Docetaxel, a known chemotherapeutic agent used in suppressing breast cancer cells in an allograft model. This makes it more promising in setting up the platform for a highly specific cancer treatment model. The combination of Docetaxel and Melittin even proved to be effective in reducing tumour growth in mice models as well. And, Melittin treatment can potentially prove to be an effective agent against other cancer types as well like Lung cancer, wherein also, the cancerous cells are characterised to over-express EGFRs and HER-2.
Since this study is mostly in vitro, hence there are still doubts over the real-world efficacy of Melittin in an in vivo condition, which is an extremely important aspect in unveiling its true clinical potentials. There’s still a long way to go before this could be accurately utilized as a treatment for humans, but this certainly ignites hope in being able to eradicate cancers with high specificity and effectivity.
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Reference:
Duffy, C., Sorolla, A., Wang, E., Golden, E., Woodward, E., Davern, K., Ho, D., Johnstone, E., Pfleger, K., Redfern, A., Iyer, K. S., Baer, B., & 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), 1–16. https://doi.org/10.1038/s41698-020-00129-0
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Good achievement for human beings. Go ahead.