BAL ARISI ( APİS MELLİFERA ) VENOMUNDAN SAFLAŞTIRILMIŞ MELİTTİN’İN U118 GLİOBLASTOMA HÜCRE HATTI ÜZERİNDEKİ ETKİLERİ

Abstract

Glioblastoma multiforme (GBM); is one of the deadly brain tumors created by the glial cells in the central nervous system defined as grade IV by the World Health Organization (WHO). MMP-9 and ADAMTS-5 are proteases that are effective in cancer cell invasion, besides TGF-β cytokines are effective in cell invasion. Due to the inadequacy of currently available cancer therapies, new agents and treatment strategies which can increase the effectiveness of chemotherapeutic drugs have started to be needed. One of the most investigated biotoxin, Melittin (MEL) is the main component of bee venom. In this study, the effects of purified melittin from honeybee (Apis mellifera) venom on U118 glioblastoma cell line was investigated. Mitokondrial activities of the melittin on the cells with MTT test, and the presence of protein component on the cells with the western blotting method have been displayed. The lowest absorbance values in U118 cells exposed to MEL at concentrations of 0.5, 1, 3, 5, 10, 15, 20 μg/ml for 1, 3, 24, 48 and 72 hours in MTT test were measured at doses of 10, 15 and 20 μg/ml. While TGF-β protein levels were low in the U118 control group cells, it was observed that TGF-β was activated by administration of low dose MEL to the cells. The activation of TGF-β has increased by the toxic effect of MEL. However; toxic effect of MEL on U118 cell increases with increased administration time, and TGF-β has been suppressed. The highest decrease in TGF-β protein level compared to U118 control cells was observed in cells treated with Melittin for 48 hours at a concentration of 3 μg/ml, and the decrease was 0.7 fold. Because of the toxic effect of Melittin, the secretion of MMP-9 protein was suppressed in cells treated with Melittin at a concentration of 3 μg/ml for 48 hours in U118 cells, and thus no band image was able to be obtained. At 24 hours of application of MEL at 3 μg/ml concentration, there was a 0.8 fold decrease in MMP-9 protein level compared to control cells. It has been identified that the ADAMTS-5 protein levels of U118 cells were lower than control cells. Comparing to the U118 control cells, the highest decrease was observed at ADAMTS-5 protein level of cells treated with Melittin for 48 hours at a concentration of 3 μg/ml, and the decrease was 0.85 fold. The protein levels of MMP-9 and ADAMTS- 5 proteases and TGF-β cytokin analysed by western blotting has been displayed the cells threated with MEL minimum level through 48 hour and 3 µg/ml concentration. The results obtained that MEL may be an alternative way for therapy of GBM cells.