Defined pulsed electro-magnetic field exposure suppresses stemness and potentiates temozolomide-induced apoptosis in glioblastoma cells

Glioblastoma is a highly aggressive brain tumor with rapid growth and poor prognosis, highlighting the need for novel therapeutic approaches. This study investigated the effects of defined low-frequency pulsed electromagnetic fields (PEMFs) on glioblastoma cells, focusing on cell viability, stemness, and drug response. Our findings demonstrate that daily exposure to a defined PEMF sequence over four days slightly reduced cell viability, while significantly downregulated the expression of POU5F1 and NANOG. Functionally, PEMF treatment inhibited neurosphere formation, significantly decreasing both their number and size. Furthermore, CDH1 expression was induced, while CD44 and ALDH1A3 expression remained unchanged, suggesting a partial mesenchymal-to-epithelial transition. Importantly, PEMF exposure enhanced the pro-apoptotic effects of the standard chemotherapeutic agent temozolomide (TMZ). Since activation of the AKT pathway is associated with resistance to TMZ, the impact of PEMF treatment on AKT activation was examined. PEMFs suppressed stemness-related gene expression without altering AKT protein levels or its phosphorylation. Notably, combining PEMF treatment with the AKT inhibitor MK-2206 caused a marked decrease in cell viability. Overall, these findings demonstrate that a precisely defined PEMF protocol selectively impairs glioblastoma cell plasticity and stem-like traits, providing a foundation for future studies into the underlying mechanisms.