Electromagnetic fields at mobile phone frequency induce apoptosis and inactivation of the multi-chaperone complex in human epidermoid cancer cells.

Abstract

The exposure to non-thermal microwave electromagnetic field (MW-EMF) at 1.95 MHz, a frequency used in mobile communication, affects the refolding kinetics of eukaryotic proteins (Mancinelli et al., 2004). On these basis we have evaluated the in vivo effect of MW-EMF in human epidermoid cancer KB cells. We have found that MW-EMF induces time-dependent apoptosis (45% after 3 h) that is paralleled by an about 2.5-fold decrease of the expression of ras and Raf-1 and of the activity of ras and Erk-1/2. Although also the expression of Akt was reduced its activity was unchanged likely as a consequence of the increased expression of its upstream activator PI3K. In the same experimental conditions an about 2.5-fold increase of the ubiquitination of ras and Raf-1 was also found and the addition for 12 h of proteasome inhibitor lactacystin at 10 microM caused an accumulation of the ubiquitinated isoforms of ras and Raf-1 and counteracted the effects of MW-EMF on ras and Raf-1 expression suggesting an increased proteasome-dependent degradation induced by MW-EMF. The exposure of KB cells to MW-EMF induced a differential activation of stress-dependent pathway with an increase of JNK-1 activity and HSP70 and 27 expression and with a reduction of p38 kinase activity and HSP90 expression. The overexpression of HSP90 induced by transfection of KB cells with a plasmid encoding for the factor completely antagonized the apoptosis and the inactivation of the ras --> Erk-dependent survival signal induced by MW-EMF. Conversely, the inhibition of Erk activity induced by 12 h exposure to 10 mM Mek-1 inhibitor U0126 antagonized the effects induced by HSP90 transfection on apoptosis caused by MW-EMF. In conclusion, these results demonstrate for the first time that MW-EMF induces apoptosis through the inactivation of the ras --> Erk survival signaling due to enhanced degradation of ras and Raf-1 determined by decreased expression of HSP90 and the consequent increase of proteasome dependent degradation.

AI evidence extraction

Main findings

In human epidermoid cancer KB cells, non-thermal MW-EMF exposure at 1.95 MHz induced time-dependent apoptosis (reported as 45% after 3 h). Exposure was associated with decreased ras and Raf-1 expression and reduced ras/Erk-1/2 activity, increased ubiquitination of ras and Raf-1 with evidence consistent with enhanced proteasome-dependent degradation, and altered stress signaling including increased JNK-1 activity and reduced p38 activity; HSP90 overexpression antagonized the MW-EMF-induced apoptosis and signaling changes.

Outcomes measured

• Apoptosis
• ras and Raf-1 expression
• ras and Erk-1/2 activity
• Akt expression and activity
• PI3K expression
• Ubiquitination of ras and Raf-1
• Proteasome-dependent degradation (lactacystin effects)
• Stress pathway signaling (JNK-1 activity, p38 kinase activity)
• Heat shock protein expression (HSP70, HSP27, HSP90)

Limitations

• In vitro cell-line study; findings may not generalize to humans or in vivo conditions
• No SAR or detailed dosimetry reported in the abstract
• Sample size/replication not reported in the abstract
• Frequency reported as 1.95 MHz in abstract (terminology includes 'microwave'); exposure characterization may be unclear from abstract alone

{
    "study_type": "in_vitro",
    "exposure": {
        "band": "microwave",
        "source": "mobile phone",
        "frequency_mhz": 1.9499999999999999555910790149937383830547332763671875,
        "sar_wkg": null,
        "duration": "up to 3 h (apoptosis reported after 3 h); additional conditions include 12 h exposures with inhibitors/transfection"
    },
    "population": "Human epidermoid cancer KB cells",
    "sample_size": null,
    "outcomes": [
        "Apoptosis",
        "ras and Raf-1 expression",
        "ras and Erk-1/2 activity",
        "Akt expression and activity",
        "PI3K expression",
        "Ubiquitination of ras and Raf-1",
        "Proteasome-dependent degradation (lactacystin effects)",
        "Stress pathway signaling (JNK-1 activity, p38 kinase activity)",
        "Heat shock protein expression (HSP70, HSP27, HSP90)"
    ],
    "main_findings": "In human epidermoid cancer KB cells, non-thermal MW-EMF exposure at 1.95 MHz induced time-dependent apoptosis (reported as 45% after 3 h). Exposure was associated with decreased ras and Raf-1 expression and reduced ras/Erk-1/2 activity, increased ubiquitination of ras and Raf-1 with evidence consistent with enhanced proteasome-dependent degradation, and altered stress signaling including increased JNK-1 activity and reduced p38 activity; HSP90 overexpression antagonized the MW-EMF-induced apoptosis and signaling changes.",
    "effect_direction": "harm",
    "limitations": [
        "In vitro cell-line study; findings may not generalize to humans or in vivo conditions",
        "No SAR or detailed dosimetry reported in the abstract",
        "Sample size/replication not reported in the abstract",
        "Frequency reported as 1.95 MHz in abstract (terminology includes 'microwave'); exposure characterization may be unclear from abstract alone"
    ],
    "evidence_strength": "low",
    "confidence": 0.7399999999999999911182158029987476766109466552734375,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "microwave electromagnetic field",
        "MW-EMF",
        "mobile communication frequency",
        "KB cells",
        "apoptosis",
        "ras",
        "Raf-1",
        "Erk1/2",
        "HSP90",
        "proteasome",
        "ubiquitination",
        "JNK",
        "p38"
    ],
    "suggested_hubs": []
}

Comments

Log in to comment.

No comments yet.