Study on in vitro therapeutic impact of 17-ꞵ Estradiol on Glioblastoma cell lines

Abstract

Glioblastomas (GBM) or grade IV astrocytomas is the most aggressive and frequent tumor in the Central Nervous System (CNS). GBM treatment mainly consists of surgical resection and radio and/or chemotherapy. However, due to its infiltration capacity, it is practically impossible to completely extract the tumor and it relapses. Aberrant EGFR expression is observed in GBM including EGFR mutation, rearrangement and deletions. Blood brain barrier is one of the major obstacles which prevents the entry of larger molecules into the brain. Hence a small molecule, with lesser neurotoxicity should be developed in treating GBM or any other brain related diseases. Previous studies have reported the therapeutic potency of 17-ꞵ Estradiol in treating breast cancer, but little is known about the therapeutic role of estrogen signalling in the development and progression of gliomas. Estradiol being the small molecule has molecular weight of 272.4g/mol. It is a lipophilic molecule and therefore it can pass through the blood brain barrier by passive diffusion and could be considered as a therapeutic molecule in treating GBM. Present study showed that 17-ꞵ Estradiol inhibited the migration, colony formation in GBM cell lines. Further it induced early and late apoptosis and arrested the cell cycle at S-Phase of the cell cycle. EGFR and downstream EGFR associated protein expression were also reduced upon exposure of GBM cell lines to E2. These results show that 17-ꞵ Estradiol could be considered as a therapeutic molecule in GBM treatment.