Distinct Epigenetic Reprogramming, Mitochondrial Patterns, Cellular Morphology and Cytotoxicity after Bee Venom Treatment

Çelik Uzuner S. , Birinci E., Tetikoğlu S., Birinci C., Kolaylı S.

Recent Patents On Anti-Cancer Drug Discovery, vol.7, pp.1-15, 2021 (Journal Indexed in SCI Expanded)

  • Publication Type: Article / Article
  • Volume: 7
  • Publication Date: 2021
  • Doi Number: 10.2174/1574892816666210422125058
  • Title of Journal : Recent Patents On Anti-Cancer Drug Discovery
  • Page Numbers: pp.1-15


Background: Bee venom is a promising agent for use in cancer treatment due to its selective cytotoxic potential for cancer cells through apoptotic pathways. However, there is no evidence for changes in epigenome and mitochondrial DNA copy numbers after bee venom application. The purpose of this study was to determine the impact of bee venom on cytosine modifications and mitochondrial DNA copy number variation.

Methods: A broad range of methods was applied to elucidate the impact of bee venom on neoplastic cells. These included MTT assay for detection of cytotoxicity, immunostaining of cytosine modifications and mitochondria, assessment of cellular morphology by flow cytometry and quantification of mitochondrial DNA copy numbers using QPCR.

Results: Bee venom-induced cell death was selective for cancer cells, where it triggered a response characterised by alteration of cytosine modification. In contrast, normal cells were more resistant to DNA modifications. Furthermore, application of the venom resulted in variation of mitochondrial membrane permeability and mitochondrial DNA copy numbers, together with alterations in cell morphology manifesting as a reduced affected cell size.

Conclusion: The study findings suggest that bee venom can be used as a selective DNA (de)methylating agent in cancer. Various agents (such as Decitabine and 5-azacytidine) have been synthesized and developed for use in cancer treatment, and a range of syntheses, and preparation and application methods have been described for these patented drugs. However, to the best of our knowledge, no previous research has investigated the use of bee venom or any component thereof for epigenetic therapy in cancer cells.