Pivotal Factors in Breast Cancer Molecular Subtypes Apoptosis Induction by ELF-EMF; Ki-67, ROS Level, HER-2, and SODs

Abstract

Background: Although increasing research has shown that extremely low-frequency electromagnetic fields (ELF-EMFs) specifically trigger PCD through the elevation of ROS levels in cancer cells, there is no adequate evidence to determine the exact mechanisms of this phenomenon. The antioxidant machinery may play a crucial role in this area; however, this has been neglected in previous research. Methods: The main aim of this study was to assess the effect of ELF-EMF exposure (5 days, 1 Hz, 100 mT, 2 h/day) on ROS levels, expression levels of antioxidant genes, and apoptosis induction in different breast cancer molecular subtypes with different p53 statuses. Results: DCFH-DA results revealed that the ROS level increased in all three cell lines (SKBR-3, MDA-MB-231, and MCF-7); this increase was much greater in SKBR-3 (up to 5-fold compared to its sham exposure). This result was concurrent with the annexin V/PI results; SKBR-3 cells showed much more apoptosis induction (about 78%), compared with the others (22% or 11% in the other two cells). On the other hand, the mRNA expression level of SOD1 and SOD2 increased significantly in the MDA-MB-231, in addition to these two genes, the expression level of SOD3 and GSR increased in the MCF-7 cells but not in the SKBR-3. Conclusion: Taken together, our results confirmed that ELF-EMF induced ROS-dependent apoptosis, especially in HER-2-enriched breast cancer cells (the SKBR-3), in a p53-independent manner. Other molecular subtypes (MDA-MB-231 as TNBC, or MCF-7 as luminal A) showed resistance against the ROS level increasing and subsequent apoptosis induction by using antioxidant genes, especially SOD1.

AI evidence extraction

Main findings

Exposure to a 1 Hz, 100 mT ELF-EMF increased ROS in all three breast cancer cell lines and induced the greatest apoptosis in SKBR-3 cells (about 78% versus 22% or 11% in the other lines). Antioxidant gene expression increased in MDA-MB-231 and MCF-7 cells but not SKBR-3 cells, supporting subtype-dependent, ROS-associated apoptosis.

Outcomes measured

• Reactive oxygen species levels
• Apoptosis measured by annexin V/PI
• SOD1, SOD2, SOD3, and GSR mRNA expression

Limitations

• In vitro cell-line study without clinical or in vivo outcomes
• Sample and replicate numbers were not reported in the abstract
• Only one exposure intensity, frequency, and schedule were described

{
    "study_type": "in_vitro",
    "exposure": {
        "band": "ELF",
        "source": null,
        "frequency_mhz": 9.99999999999999954748111825886258685613938723690807819366455078125e-7,
        "sar_wkg": null,
        "duration": "5 days, 2 hours/day"
    },
    "population": "Human breast cancer cell lines SKBR-3 (HER-2-enriched), MDA-MB-231 (triple-negative), and MCF-7 (luminal A)",
    "sample_size": null,
    "outcomes": [
        "Reactive oxygen species levels",
        "Apoptosis measured by annexin V/PI",
        "SOD1, SOD2, SOD3, and GSR mRNA expression"
    ],
    "main_findings": "Exposure to a 1 Hz, 100 mT ELF-EMF increased ROS in all three breast cancer cell lines and induced the greatest apoptosis in SKBR-3 cells (about 78% versus 22% or 11% in the other lines). Antioxidant gene expression increased in MDA-MB-231 and MCF-7 cells but not SKBR-3 cells, supporting subtype-dependent, ROS-associated apoptosis.",
    "effect_direction": "benefit",
    "limitations": [
        "In vitro cell-line study without clinical or in vivo outcomes",
        "Sample and replicate numbers were not reported in the abstract",
        "Only one exposure intensity, frequency, and schedule were described"
    ],
    "evidence_strength": "low",
    "confidence": 0.95999999999999996447286321199499070644378662109375,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "ELF-EMF",
        "breast cancer",
        "apoptosis",
        "reactive oxygen species",
        "HER-2",
        "SKBR-3",
        "MDA-MB-231",
        "MCF-7",
        "SOD1",
        "SOD2",
        "SOD3",
        "GSR",
        "p53"
    ],
    "suggested_hubs": []
}

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