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

Journal of cellular physiology · 2005 · Harm · Low evidence

← Research stream

HarmLow evidencePaper 5198

Study snapshot

PublicationJournal of cellular physiology · 2005

Study typein_vitro

Reported directionHarm

Evidence ratingLow

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.

Machine Enhanced Logic

AI evidence extraction

Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.

Study typein_vitro

Effect directionharm

PopulationHuman epidermoid cancer KB cells

Sample sizeNot supplied

Exposuremicrowave · 1.95 MHz · up to 3 h (apoptosis reported after 3 h); additional conditions include 12 h exposures with inhibitors/transfection

Evidence strengthLowConfidence: 74% · Peer reviewed: yes

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

View raw extracted JSON

{
  "study_type": "in_vitro",
  "exposure": {
    "band": "microwave",
    "source": "mobile phone",
    "frequency_mhz": 1.95,
    "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": 0.74,
  "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": []
}

AI can be wrong. Always verify against the paper.

AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.

Identifiers and source

DOI: 10.1002/jcp.20327
PubMed: 15754340

Read the original paper →

Related papers

← Back to the Research Library