Investigation of the synergistic effect of pulsed electromagnetic field exposure and resveratrol on apoptotic pathway in glioblastoma cells

Glioblastoma multiforme (GBM) is the most common malignant astrocytic brain tumor in adults and, despite the variety of modern treatments, it remains a lethal disease. Pulsed magnetic field (PEMF) is a low-frequency electromagnetic field that does not have ionizing or thermal effects and has reported numerous therapeutic effects. Resveratrol (RES) is a naturally occurring polyphenolic compound that has numerous therapeutic effects. In the literature, there are limited studies that assess the effects of PEMF exposure and resveratrol on brain cancer cells together. In particular, there are almost no studies examining the possible effects of PEMF exposure along with RES on the apoptotic pathway in glioblastoma. Hence, the synergistic effects of resveratrol and PEMF exposure on cell viability, the pathways leading to cell death (apoptosis/necrosis), and the expression levels of key genes and proteins involved in both pro-apoptotic and PI3K/AKT/mTOR intracellular signaling pathways in the human glioblastoma U87MG cell line were investigated using Alamar Blue, Flow Cytometry, qRT-PCR, and Western blot techniques in this thesis. Overall data reported that 6 hours of PEMF exposure following RES treatment triggered apoptosis in the U87-MG cell line by reducing cell viability and increasing the expressions of caspase-9, caspase-3, bax/BcL-2, TP53 and P53. Although PI3K, AKT, and mTOR expressions were elevated, their increase was less pronounced compared to the main apoptotic genes and proteins, suggesting these pathways may still inhibit the apoptotic response. Comparisons with temozolomide (TMZ) show that the RES-PEMF combination produces a stronger cellular response than the TMZ-PEMF combination. Scientific findings suggest that resveratrol and PEMF may synergistically enhance apoptosis in glioblastoma cells and could serve as a potential alternative cancer therapy, including for glioblastoma. We believe that this study will provide an important basis for future clinical and biomedical research, especially in which the synergistic effects of RES and PEMF will be evaluated in a broader spectrum.