Exposure to a specific time-varying electromagnetic field inhibits cell proliferation via cAMP and ERK signaling in cancer cells

Abstract

Exposure to a specific time-varying electromagnetic field inhibits cell proliferation via cAMP and ERK signaling in cancer cells Buckner CA, Buckner AL, Koren SA, Persinger MA, Lafrenie RM. Exposure to a specific time-varying electromagnetic field inhibits cell proliferation via cAMP and ERK signaling in cancer cells. Bioelectromagnetics. 2017 Nov 10. doi: 10.1002/bem.22096. Abstract Exposure to specific electromagnetic field (EMF) patterns can affect a variety of biological systems. We have shown that exposure to Thomas-EMF, a low-intensity, frequency-modulated (25-6 Hz) EMF pattern, inhibited growth and altered cell signaling in malignant cells. Exposure to Thomas-EMF for 1 h/day inhibited the growth of malignant cells including B16-BL6 mouse melanoma cells, MDA-MB-231, MDA-MB-468, BT-20, and MCF-7 human breast cancer and HeLa cervical cancer cells but did not affect non-malignant cells. The Thomas-EMF- dependent changes in cell proliferation were mediated by adenosine 3',5'-cyclic monophosphate (cAMP) and extracellular-signal-regulated kinase (ERK) signaling pathways. Exposure of malignant cells to Thomas-EMF transiently changed the level of cellular cAMP and promoted ERK phosphorylation. Pharmacologic inhibitors (SQ22536) and activators (forskolin) of cAMP production both blocked the ability of Thomas-EMF to inhibit cell proliferation, and an inhibitor of the MAP kinase pathway (PD98059) was able to partially block Thomas-EMF- dependent inhibition of cell proliferation. Genetic modulation of protein kinase A (PKA) in B16-BL6 cells also altered the effect of Thomas-EMF on cell proliferation. Cells transfected with the constitutively active form of PKA (PKA-CA), which interfered with ERK phosphorylation, also interfered with the Thomas-EMF effect on cell proliferation. The non-malignant cells did not show any EMF-dependent changes in cAMP levels, ERK phosphorylation, or cell growth. These data indicate that exposure to the specific Thomas-EMF pattern can inhibit the growth of malignant cells in a manner dependent on contributions from the cAMP and MAP kinase pathways. ncbi.nlm.nih.gov

AI evidence extraction

Main findings

Exposure to a low-intensity, frequency-modulated Thomas-EMF pattern (25–6 Hz) for 1 h/day inhibited growth of multiple malignant cell lines (mouse melanoma; human breast cancer and cervical cancer cells) but did not affect non-malignant cells. In malignant cells, exposure transiently changed cAMP levels and promoted ERK phosphorylation; pharmacologic and genetic modulation of cAMP/PKA and MAPK signaling blocked or partially blocked the EMF-associated inhibition of proliferation.

Outcomes measured

• Cell proliferation/growth in malignant vs non-malignant cells
• Cellular cAMP levels
• ERK phosphorylation (MAP kinase pathway activity)
• Effect modification by pharmacologic modulators of cAMP (SQ22536, forskolin) and MAPK inhibitor (PD98059)
• Effect modification by genetic modulation of PKA (constitutively active PKA)

Limitations

• No exposure intensity or dosimetry metrics (e.g., field strength, SAR) reported in the abstract
• In vitro cell culture study; generalizability to in vivo or human outcomes not addressed in the abstract
• Sample sizes and experimental replication not reported in the abstract

{
    "study_type": "in_vitro",
    "exposure": {
        "band": "ELF",
        "source": null,
        "frequency_mhz": null,
        "sar_wkg": null,
        "duration": "1 h/day"
    },
    "population": null,
    "sample_size": null,
    "outcomes": [
        "Cell proliferation/growth in malignant vs non-malignant cells",
        "Cellular cAMP levels",
        "ERK phosphorylation (MAP kinase pathway activity)",
        "Effect modification by pharmacologic modulators of cAMP (SQ22536, forskolin) and MAPK inhibitor (PD98059)",
        "Effect modification by genetic modulation of PKA (constitutively active PKA)"
    ],
    "main_findings": "Exposure to a low-intensity, frequency-modulated Thomas-EMF pattern (25–6 Hz) for 1 h/day inhibited growth of multiple malignant cell lines (mouse melanoma; human breast cancer and cervical cancer cells) but did not affect non-malignant cells. In malignant cells, exposure transiently changed cAMP levels and promoted ERK phosphorylation; pharmacologic and genetic modulation of cAMP/PKA and MAPK signaling blocked or partially blocked the EMF-associated inhibition of proliferation.",
    "effect_direction": "benefit",
    "limitations": [
        "No exposure intensity or dosimetry metrics (e.g., field strength, SAR) reported in the abstract",
        "In vitro cell culture study; generalizability to in vivo or human outcomes not addressed in the abstract",
        "Sample sizes and experimental replication not reported in the abstract"
    ],
    "evidence_strength": "low",
    "confidence": 0.7800000000000000266453525910037569701671600341796875,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "Thomas-EMF",
        "time-varying electromagnetic field",
        "frequency-modulated",
        "25–6 Hz",
        "low-intensity",
        "cell proliferation",
        "cAMP",
        "ERK phosphorylation",
        "MAP kinase",
        "PKA",
        "cancer cells",
        "Bioelectromagnetics"
    ],
    "suggested_hubs": []
}

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