Cytotoxicity of temozolomide on human glioblastoma cells is enhanced by the concomitant exposure to an extremely low-frequency electromagnetic field (100Hz, 100G).

Abstract

Glioblastoma multiforme (GBM) is the most malignant brain cancer that causes high mortality in humans. It responds poorly to the most common cancer treatments, such as surgery, chemo- and radiation therapy. Temozolomide (TMZ) is an alkylating agent that has been widely used to treat GBM; resistance to this drug is often found. One unexplored possibility for overcoming this resistance is a treatment based on concomitant exposure to electromagnetic fields (EMF) and TMZ. Indeed, many evidences show that EMF affects cancer cells and drug performance. In this study, we evaluated the potential synergistic effect of 100μM TMZ and EMF (100Hz, 100G) on two human glioma cells line, i.e., U87 and T98G above single treatments, TMZ or EMF. Co-treatment synergistically enhanced apoptosis in U87 and T98G cells, by increasing the expression of P53, Bax, and Caspase-3 and decreasing that of Bcl-2 and Cyclin-D1. We also observed an increase in reactive oxygen species (ROS) production and the overexpression of the heme oxygenase-1 (HO-1) gene in comparison to controls. In conclusion, since EMF enhanced the apoptotic effect of TMZ, possibly through a redox regulation mechanism, the TMZ/EMF combination may be effective for glioma cancer treating. Further studies are needed to reveal the action mechanism of this possible novel therapeutic approach.

AI evidence extraction

Main findings

In two human glioma cell lines (U87 and T98G), co-treatment with temozolomide (100 μM) and an extremely low-frequency electromagnetic field (100 Hz, 100 G) increased apoptosis compared with temozolomide or EMF alone. The co-treatment increased P53, Bax, and Caspase-3 expression, decreased Bcl-2 and Cyclin-D1, and was associated with increased ROS production and HO-1 overexpression versus controls.

Outcomes measured

• Apoptosis
• Expression of P53, Bax, Caspase-3, Bcl-2, Cyclin-D1
• Reactive oxygen species (ROS) production
• HO-1 gene expression

Limitations

• In vitro study in glioma cell lines (U87, T98G); findings may not translate to humans.
• Exposure duration not reported in the abstract.
• Sample size/replicates not reported in the abstract.
• Mechanism described as possible; further studies needed per authors.

{
    "study_type": "in_vitro",
    "exposure": {
        "band": "ELF",
        "source": null,
        "frequency_mhz": 0.000100000000000000004792173602385929598312941379845142364501953125,
        "sar_wkg": null,
        "duration": null
    },
    "population": null,
    "sample_size": null,
    "outcomes": [
        "Apoptosis",
        "Expression of P53, Bax, Caspase-3, Bcl-2, Cyclin-D1",
        "Reactive oxygen species (ROS) production",
        "HO-1 gene expression"
    ],
    "main_findings": "In two human glioma cell lines (U87 and T98G), co-treatment with temozolomide (100 μM) and an extremely low-frequency electromagnetic field (100 Hz, 100 G) increased apoptosis compared with temozolomide or EMF alone. The co-treatment increased P53, Bax, and Caspase-3 expression, decreased Bcl-2 and Cyclin-D1, and was associated with increased ROS production and HO-1 overexpression versus controls.",
    "effect_direction": "benefit",
    "limitations": [
        "In vitro study in glioma cell lines (U87, T98G); findings may not translate to humans.",
        "Exposure duration not reported in the abstract.",
        "Sample size/replicates not reported in the abstract.",
        "Mechanism described as possible; further studies needed per authors."
    ],
    "evidence_strength": "low",
    "confidence": 0.7800000000000000266453525910037569701671600341796875,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "glioblastoma multiforme",
        "glioma",
        "temozolomide",
        "extremely low-frequency electromagnetic field",
        "100 Hz",
        "100 G",
        "apoptosis",
        "ROS",
        "HO-1",
        "P53",
        "Bax",
        "Caspase-3",
        "Bcl-2",
        "Cyclin-D1"
    ],
    "suggested_hubs": []
}

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