P53 status, and G2/M cell cycle arrest, are determining factors in cell-death induction mediated by ELF-EMF in glioblastoma.

Abstract

The average survival of patients with glioblastoma is 12-15 months. Therefore, finding a new treatment method is important, especially in cases that show resistance to treatment. Extremely low-frequency electromagnetic fields (ELF-EMF) have characteristics and capabilities that can be proposed as a new cancer treatment method with low side effects. This research examines the antitumor effect of ELF-EMF on U87 and U251 glioblastoma cell lines. Flowcytometry determined the viability/apoptosis and distribution of cells in different phases of the cell cycle. The size of cells was assessed by TEM. Important cell cycle regulation genes mRNA expression levels were investigated by real-time PCR. ELF-EMF induced apoptosis in U87cells much more than U251 (15% against 2.43%) and increased G2/M cell population in U87 (2.56%, p value < 0.05), and S phase in U251 (2.4%) (data are normalized to their sham exposure). The size of U87 cells increased significantly after ELF-EMF exposure (overexpressing P53 in U251 cells increased the apoptosis induction by ELF-EMF). The expression level of P53, P21, and MDM2 increased and CCNB1 decreased in U87. Among the studied genes, MCM6 expression decreased in U251. Increasing expression of P53, P21 and decreasing CCNB1, induction of cell G2/M cycle arrest, and consequently increase in the cell size can be suggested as one of the main mechanisms of apoptosis induction by ELF-EMF; furthermore, our results demonstrate the possible footprint of P53 in the apoptosis induction by ELF-EMF, as U87 carry the wild type of P53 and U251 has the mutated form of this gene.

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Main findings

ELF-EMF exposure induced apoptosis in U87 glioblastoma cells more than in U251 cells (15% vs 2.43%, normalized to sham). ELF-EMF increased the G2/M cell population in U87 (2.56%, p<0.05) and increased the S-phase population in U251 (2.4%); U87 cell size increased significantly after exposure. Gene expression changes included increased P53, P21, and MDM2 and decreased CCNB1 in U87, and decreased MCM6 in U251; overexpressing P53 in U251 increased ELF-EMF–induced apoptosis.

Outcomes measured

• Apoptosis/viability (flow cytometry)
• Cell cycle phase distribution (G2/M, S phase)
• Cell size (TEM)
• mRNA expression of cell-cycle regulation genes (real-time PCR): P53, P21, MDM2, CCNB1, MCM6

Limitations

• Exposure parameters (e.g., frequency, field strength, duration) are not provided in the abstract.
• In vitro study in two glioblastoma cell lines; clinical relevance is not established in the abstract.
• Sample size/replicates are not reported in the abstract.

{
    "study_type": "in_vitro",
    "exposure": {
        "band": "ELF",
        "source": null,
        "frequency_mhz": null,
        "sar_wkg": null,
        "duration": null
    },
    "population": null,
    "sample_size": null,
    "outcomes": [
        "Apoptosis/viability (flow cytometry)",
        "Cell cycle phase distribution (G2/M, S phase)",
        "Cell size (TEM)",
        "mRNA expression of cell-cycle regulation genes (real-time PCR): P53, P21, MDM2, CCNB1, MCM6"
    ],
    "main_findings": "ELF-EMF exposure induced apoptosis in U87 glioblastoma cells more than in U251 cells (15% vs 2.43%, normalized to sham). ELF-EMF increased the G2/M cell population in U87 (2.56%, p<0.05) and increased the S-phase population in U251 (2.4%); U87 cell size increased significantly after exposure. Gene expression changes included increased P53, P21, and MDM2 and decreased CCNB1 in U87, and decreased MCM6 in U251; overexpressing P53 in U251 increased ELF-EMF–induced apoptosis.",
    "effect_direction": "mixed",
    "limitations": [
        "Exposure parameters (e.g., frequency, field strength, duration) are not provided in the abstract.",
        "In vitro study in two glioblastoma cell lines; clinical relevance is not established in the abstract.",
        "Sample size/replicates are not reported in the abstract."
    ],
    "evidence_strength": "low",
    "confidence": 0.7800000000000000266453525910037569701671600341796875,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "ELF-EMF",
        "extremely low-frequency electromagnetic fields",
        "glioblastoma",
        "U87",
        "U251",
        "apoptosis",
        "cell cycle arrest",
        "G2/M",
        "P53",
        "P21",
        "MDM2",
        "CCNB1",
        "MCM6",
        "TEM",
        "flow cytometry",
        "real-time PCR"
    ],
    "suggested_hubs": []
}

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