The Comparative Cytotoxic Effects of Apis mellifera Crude Venom on MCF-7 Breast Cancer Cell Line in 2D and 3D Cell Cultures

Abstract

Bee venom (BV) has variety of properties, such as anti-inflammatory potential and anti-cancer activity.It has been shown that BV has cytotoxic effects on MCF-7 cells in 2D culture. Cell encapsulation is one of the three-dimensional (3D) culture methods that can better represent the physiological conditions of natural tissues and tumors in comparison to two-dimensional (2D) culture. However, the effect of BC on 3D culture has yet studied. The present study was designed to compare the cytotoxic effects of BV on MCF-7 cells in 3D and 2D cultures for the first time. To this purpose, the MCF-7 cells were encapsulated to create a 3D culture using alginate hydrogel, a natural polysaccharide. Cytotoxicity effect of BV was investigated using 3-(4,5-Dimethylthiazoyl-2-yl)-2,5-Diphenyltetrazolium bromide (MTT) reduction and confirmed with neutral red uptake assay following venom exposure. Apoptosis was evaluated with reactive nitrogen species assay, measuring Caspase-3 activity and Comet assay. Moreover, oxidative stress was evaluated by glutathione (GSH) and catalase assays. Results of caspase-3 and comet assays showed an increase of tumoral cells apoptosis following the treatment with venom in a dose dependent manner in both 2D and 3D cultures. GSH and catalase measurements showed that oxidative stress was increased in MCF-7 cells treated with BV in a dose dependent manner in both 2D and 3D cultures. The results of the present study show that the crude venom of Apis mellifera has cytotoxic effects on MCF-7 cells in a dose dependent manner. Indeed, it was shown that the effect of the venom on MCF-7 cells in 2D culture is significantly higher than that of the 3D culture.