Pulsed Electromagnetic Fields Enhance Resveratrol-Induced Apoptosis Through Modulation of Apoptotic Signaling in...

Glioblastoma multiforme (GBM) is an aggressive primary brain tumor characterized by dysregulated cellular signaling and resistance to apoptosis. Pulsed electromagnetic field (PEMF) exposure has been reported to modulate cancer-related cellular processes, while resveratrol (RES), a natural polyphenol, exhibits notable antiproliferative and pro-apoptotic actions. Here, we investigated whether 75 Hz PEMF potentiates RES-mediated apoptosis in human glioblastoma U87-MG cells by examining key molecules involved in apoptotic signaling and the transcriptional responses of PI3K/AKT/mTOR pathway-related genes. U87-MG glioblastoma cells and non-tumour human astroglial SVG-P12 cells were cultured and divided into the following six groups: (I) untreated cells; (II) RES-treated cells; (III) temozolomide (TMZ)-treated cells; (IV) PEMF-exposed cells; (V) cells treated with RES followed by PEMF exposure; and (VI) cells treated with TMZ followed by PEMF exposure. Cell viability was assessed in both cell lines by alamar blue assay, and selectivity indices were derived from the resulting IC50 values. Apoptotic responses and gene expression profiles were assessed in U87-MG cells by flow cytometry and qRT-PCR, while selected apoptosis-related proteins were evaluated by Western blotting. RES treatment induced stronger cytotoxic effects than TMZ in U87-MG cells, and this response was markedly enhanced following PEMF exposure, the IC₅₀ falling from 33.64 to 10.53 µg/mL. In SVG-P12 astroglia the IC₅₀ of RES rose from 17.95 to 98.31 µg/mL under the same exposure, so that the selectivity index of RES increased from 0.53 to 9.34, whereas that of TMZ remained essentially unchanged (1.54 versus 1.50). Combined RES and PEMF treatment significantly increased both early and late apoptosis. Molecular analyses revealed upregulation of pro-apoptotic markers accompanied by an increased Bax/BcL-2 ratio, consistent with protein-level changes. Transcripts of PI3K/AKT/mTOR pathway-related components were also elevated relative to untreated cells, but to a markedly lesser extent than the apoptotic markers. PEMF exposure significantly enhances the pro-apoptotic effects of RES in glioblastoma cells while relatively preserving SVG-P12 cell viability, supporting further investigation of this combination as a potential adjuvant approach.