Electromagnetic Field and Temozolomide Increase Differentiation of Human Glioblastoma Cell Line; concise view of mechanism

Glioblastoma is a highly malignant brain tumor with an extremely dismal prognosis, with a median survival of 12 months. Promoting glioma stem cell (GSC) differentiation is a crucial therapeutic strategy in treating glioblastoma to improve survival. We combine standard chemotherapy drug Temozolomide (TMZ) with Electromagnetic Field to evaluate their differentiation effects on glioma U87 cell line.Human glioma U87 cells exposed to electromagnetic field (EMF), Temozolomide (TMZ) alone and a combination of both were compared to control group. Nestin and CD133 were detected to identify stem-like cells (SLCs) changes during the experiment. The differentiation was found through detecting the expression of the glial fibrillary acidic protein (GFAP), and Notch4. We evaluated Ca+, SOD, and Notch as important chemical mediators in signal transduction to elucidate the mechanism of actions in the processes of differentiation.The expression of cancer SLC markers CD133, and neural stem/progenitor Nestin decreased in EMF/ Drug combined group compared to control which shows depletion of stem-like cell pool. In contrast, the differentiation of SLCs was increased by detecting the expression of the glial fibrillary acidic protein (GFAP), but, Notch4 decreased in Electromagnetic field/Drug combined group compared to control which shows a benign process of treatment. The differentiation was also confirmed by light microscopy. Morphological changes such as an elongated shape with elongated neurites, intercellular connection, and neurite branching were observed. Superoxide dismutase (SOD), Ca+ and Notch were also increased as important chemical mediators in signal transduction. Here, we found the combination of pulsed electromagnetic fields (PEMFs) and TMZ significantly resulted in differentiation and glioma stem cells (GSCs) pool reduction that could have a profound therapeutic implication.