Akademik Veri Yönetim Sistemi
KOLAYLI S. (Yürütücü), ÇELİK UZUNER S.
TÜBİTAK Projesi, 2018 - Devam Ediyor
Bee venom (apitoxin) is an important mixture providing self-defense of honey bees. This is also a promising natural mixture for treatment of range diseases such cancer. In this study, the effects of bee venom of Anatolian honey bee on cytotoxicity and epigenetic properties in cancer cells including metastatic breast cancer (MDA-MB231) and liver cancer (HEPG2) cell lines were investigated compared to healthy fibroblast (NIH3T3) cells. The cytotoxic effect of bee venom was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Mitochondrial membrane potential (MMP) was analyzed by MitoTracker staining and the profiles of apoptotic and necrotic cells were investigated by Annexin V/PI using flow cytometer. This study is also the first study that revealed the effect of bee venom on the mechanisms of epigenetic modifications (DNA methylation) in cancer and normal cells. After bee venom, DNA methylation was labelled by immunostaining method and the levels of methylation were determined by flow cytometry in all three cells. The findings showed that i) the bee venom used in the study destroyed cancer cells more selectively than normal cells, ii) mitochondrial membrane potential that is one of the important parameters for the activity of mitochondria varied in cells after bee venom iii) cell sizes and cell granularity decreased, namely cellular morphology differed and iv) the amount of DNA methylation changed according to the cell type.
As a result, it was determined that bee venom selectively induced cell death in cancer cells and that the cells responded to bee venom in a dose-dependent manner mostly through the changes in DNA methylation, but this epigenetic response was not directly associated with the level of toxicity after bee venom. It was concluded that bee venom has the potential to be used as a demethylating agent for certain cancers and this should be supported by further in vivo studies.