Anti-cancer Activities of Honey Bee Products

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1.    INTRODUCTION

Bees are flying insects in the order Hymenoptera and are closely related to wasps and ants. They are also known commercially for their role in producing natural products, for example, Beewax, Bee pollen and Propolis. Cancer is one of the major ailment affecting humankind and remsins as one of the leading cause of mortality worldwide. Most recent studies have been found that several bee products have potential anticancer activity in vitro and in vivo. Several recent studies have reported that some natural bee products inhibit tumour cell growth (Premratanachai & Chanchao, 2014). Although pure bee venom, Apitoxin is mostly described to mediate Anti-inflammatory and Anticancer effects. (Aufschnaiter, et al., 2020). Melittin, an amphipathic 26-residues peptide is the main component of honey bee venom. This agent has shown a variety of anticancer effects in all cell culture and animal model systems (Rady, et al., 2017).

 

2.    MOLECULAR MECHANISM OF HONEY

The molecular mechanism resulting in the antiproliferative and anticancer effects of honey include cell cycle arrest, activation of mitochondrial pathway, induction of mitochondrial outer membrane permeabilization, induction of apoptosis, modulation of oxidative stress, reduction of inflammation, modulation of insulin signalling and inhibition of angiogenesis in cancer cells. Honey also shows potential effects on cancer by modulating proteins, genes, and cytokines that promote cancer.

 

3.    ANTICANCER ACTIVITIES OF PROPOLIS

Propolis (bee glue) is obtained by a bee from resins collected from trees. It is a rich mixture of polyphenols, flavonoid, phenolic, acid and their ester and phenolic aldehyde and ketones. Artepillin C isolated from propolis was reported to induce cytotoxicity of malignant melanoma cells by apoptosis the tumour growth suppression was likely to be due to its own direct cytotoxicity as well as enhanced immunity and inhibition of lipid per-oxidants.

  • Other compound from propolis (PM3) inhibits the in vivo growth of MCF-7 breast cancer cells and induce apoptosis.
  • Chrysin another bioactive compound of honey that is found propolis, has been shown to have significant biological and pharmacological properties that include Anti-inflammatory effect as well as anticancer property.
  • Chrysin influences the apoptotic process in many types of cells line, especially leukaemia and induce apoptosis by activation of caspases, suppressor of anti-apoptotic proteins such as phosphoinositide 3-kinase signal pathway (Premratanachai & Chanchao, 2014).
  • Chrysin inhibits tumour growth through apoptosis related to the activation of Notch 1 signalling pathway, both in vitro and in vivo.
  • The primary mechanism of action of chrysin consist of a decrease in cell proliferation, induction of cell death by apoptosis and reduction of inflammation.
  • Chrysin is a potential candidate for the prevention of renal carcinogenesis as it restrains several biomarkers of tumour promotion and inflammation during renal carcinogenesis (Mani & Natesan, 2018)

  Figure 1 Chrysin: Pharmacological and therapeutic properties (Naz, et al., 2019)

4.    HONEY BEE VENOM IN CANCER THERAPY

Bee venom produced in the venom gland located in the abdominal cavity contains several biologically active peptides including melittin, apamin, adolapin and several enzymes non-peptides components also obtained such as histamine, phospholipase and dopamine. Bee venom inhibits the proliferation of carcinoma of the local cellular immune response in lymph nodes The mechanism of action of bee venom include apoptosis and lysis of tumour cells.

  • Bee venom has been shown to directly inhibit the invasive and migratory ability of human breast cancer MCF-7 cells and this could be mimicked by melittin (Premratanachai & Chanchao, 2014).
  • Melittin is a 26 amino acid long amphipathic peptide and a major component of apitoxin, induce cell death by disrupting biological membrane via the formation of pores and has haemolytic effects, suggesting a non-specific controlling of this peptide (Aufschnaiter, et al., 2020).
  • Melittin modulated the signalling in breast cancer cells by suppressing the activation of the receptor that is commonly overexpressed in triple-negative, breast cancer and epidermal growth factor receptor.
  • Chemotherapies (docetaxel) with the addition of melittin can be effectively treated aggressive breast cancer in mice (Rady, et al., 2017).
  • A study showed that isolated melittin from Apis mellifera meda venom inhibited the proliferation of Hela cells and induced apoptosis on them.
  • Furthermore melittin prevents liver cancer metastasis through inhibition of the Rac-1-Dependent pathway.
  • A study also has proven that melittin (MTT assay) inhibited the proliferation of Hela cell line in a dose and time-dependent manner.
  • Cervical cancer classified as a second most common cancer between women worldwide and in many poor countries. In several studies anticancer effect of melittin on human cervical cancer line was evaluated through the induction of apoptosis
  • Several nanotechnologies mediate conjugates of melittin have already been successfully synthesized and tested in a variety of human cancer in preclinical models (Zarrinnahad, et al., 2017).


5.    CONCLUSIONS AND FUTURE PROSPECTS

Natural compounds are one of the significant consideration for the treatment of cancers, several studies have been demonstrated that melittin has an inhibitory effect on various cancer line including breast cancer, liver cancer and influence the process of apoptosis so the anticancer the activity of melittin should be future studied and developed as an alternative the approach of cancer therapy If successful, this approach could be excellent value in any part of the world where expensive chemotherapies drug is not available in the health care system.


By: Fatimah Khursheed


REFERENCES

  • Aufschnaiter, A., El-Whed, A.A., Du, M., El-Seedi, H., & Buttner, S. (2020). Apitoxin and Its Components against Cancer, Neurodegeneration and Rheumatoid Arthritis: Limitations and Possibilities. Toxins, 12(2), 66. https://doi.org/10.3390/toxins12020066
  • Mani, R., & Natesan, V. (2018).Chrysin: Sources, Beneficial Pharmacological Activities and Molecular Mechanism of Action. Phytochemistry, 145,187-196. https://doi.org/10.1016/j.phytochem.2017.09.016
  • Naz, S., Imran, m., Rauf, A., Orhan, I. E., Shariati, M. A., Iahtisham-ul-Haq,… Heydari, M. (2019) Chrysin: Pharmacological and therapeutic properties. Life sciences, 235, 116797. https://doi.org/10.1016/j.1fs.2019.116797
  • Premratanachai, P., & Chanchao, C. (2014) Review of the anticancer activities of bee products. Asian Pacific Journal of Tropical Biomedicine, 4(5) 337-344. https://doi.org/10.12980/apjtb.4.2014c1262
  • Rady, M., Siddique I. A., & Mukhtar, H. (2017). Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy. Cancer letters, 402, 16-31. https://doi.org/10.1016/j.canlet.2017.05.010
  • Zarrinnahad, H., Hamidi, M.P., Mahdavi, M., Moradi, A., Bagheri, K.P. & Shahbazzadeh, D. (2017). Apipototic Effect of Melittin Purified From Iranian Honey Bee Venom Oln Human Cervical Cancer Hela Cell Line. International Journal of Peptide Research and Therapeutics, 24(4), 563-570. https://doi.org/10.1007/s10989-0179641-1




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