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. 2016 Dec 13;11(12):e0167931.

doi: 10.1371/journal.pone.0167931. eCollection 2016.

BEMER Electromagnetic Field Therapy Reduces Cancer Cell Radioresistance by Enhanced ROS Formation and Induced Dna Damage

Affiliations

• PMID: 27959944
• PMCID: PMC5154536
• DOI: 10.1371/journal.pone.0167931

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BEMER Electromagnetic Field Therapy Reduces Cancer Cell Radioresistance by Enhanced ROS Germination and Induced DNA Damage

Katja Storch  et al. PLoS One. 2016 .

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Abstract

Each year more 450,000 Germans are expected to exist diagnosed with cancer subsequently receiving standard multimodal therapies including surgery, chemotherapy and radiotherapy. On tiptop, molecular-targeted agents are increasingly administered. Owing to intrinsic and acquired resistance to these therapeutic approaches, both the better molecular understanding of tumor biological science and the consideration of alternative and complementary therapeutic back up are warranted and open up upwardly broader and novel possibilities for therapy personalization. Specially the latter is underpinned by the increasing utilization of non-invasive complementary and alternative medicine by the population. One investigated approach is the application of low-dose electromagnetic fields (EMF) to modulate cellular processes. A detail system is the BEMER therapy as a Concrete Vascular Therapy for which a normalization of the microcirculation has been demonstrated by a low-frequency, pulsed EMF pattern. Open up remains whether this EMF pattern impacts on cancer jail cell survival upon treatment with radiotherapy, chemotherapy and the molecular-targeted amanuensis Cetuximab inhibiting the epidermal growth cistron receptor. Using more physiological, three-dimensional, matrix-based cell civilization models and cancer prison cell lines originating from lung, head and cervix, colorectal and pancreas, we bear witness significant changes in distinct intermediates of the glycolysis and tricarboxylic acid cycle pathways and enhanced cancer prison cell radiosensitization associated with increased DNA double strand intermission numbers and higher levels of reactive oxygen species upon BEMER handling relative to controls. Intriguingly, exposure of cells to the BEMER EMF pattern failed to result in sensitization to chemotherapy and Cetuximab. Further studies are necessary to better understand the mechanisms underlying the cellular alterations induced by the BEMER EMF pattern and to clarify the awarding areas for human disease.

Conflict of interest statement

The BEMER Int. AG had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Importantly, this does besides not affect our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig one. BEMER device and application.

(A) The electromagnetic field (EMF) with a pulse-elapsing of 30 ms and a pulse-frequency of 30 Hz was generated past a commercially available control unit of measurement B.Box Classic (BEMER AG Int.) with ten different levels of magnetic field intensity (from 0 μT to 35 μT). (B) The mattress applicator with a flat coil system specifically designed for cell culture. (C) Mattress applicator measurements and scheme of how cell culture plates were placed for BEMER therapy (red rectangles).

Fig 2. The specific BEMER EMF design impacts on cancer jail cell metabolism.

(A) Pie nautical chart showing the number of detected metabolites categorized by pathways (Σ 225). (B) Heatmap comparing levels of metabolites in BEMER point treated (~thirteen μT, eight min) and BEMER sham-treated (sham) A549 cells. Reddish and bluish indicate up- and downregulation, respectively. Cells were cultured in 3D lrECM for 24 h prior to BEMER treatment. (C) Amount of indicated metabolites in A549 cells without (sham) and with BEMER EMF exposure. (D) Scheme of glycolysis and TCA cycle. Metabolites in blue were downregulated, in red upregulated and in black unaffected upon BEMER therapy compared with sham-treated controls. Metabolites depicted in green were not measured in the metabolome assay. All results correspond mean ± SD. Student's t-examination. north = 5. * P < 0.05; ** P < 0.01.

Fig 3. BEMER therapy mediates radiosensitization of cancer cells.

(A) Stage contrast images and (B) basal surviving fraction of 3D grown colonies of BEMER treated (~13 μT, 8 min, 1 h, 24 h) and BEMER sham-treated (sham) cancer cell lines. (C) Period chart of colony formation assay. (D) Clonogenic prison cell survival after BEMER therapy (~13 μT, 8 min, 1 h, 24 h) combined with radiotherapy (2 and 6 Gy). All results represent mean ± SD. Student'due south t-test. n = 3. * P < 0.05; ** P < 0.01.

Fig four. BEMER therapy radiosensitizes microtumors.

(A) Flow chart of colony germination analysis. (B) Basal surviving fraction of BEMER (~xiii μT, 8 min, 1 h, 24 h) treated and BEMER sham-treated (sham) microtumors. (C) Clonogenic survival after BEMER therapy (~xiii μT, 8 min, 1 h, 24 h) combined with radiotherapy (2 and 6 Gy). All results represent hateful ± SD. Student'southward t-test compares BEMER therapy versus sham samples. n = iii. * P < 0.05; ** P < 0.01.

Fig five. BEMER therapy-mediated radiosensitization depends on treatment intervals and frequency.

(A) Flow nautical chart of colony formation analysis. (B) Clonogenic survival after BEMER therapy (~xiii μT, 8 min) combined with 6-Gy irradiation of indicated jail cell lines. BEMER sham-treated (sham) and irradiated cells served as control. Time intervals of 0, 1, 6, and 24 h between BEMER therapy and radiotherapy were practical. (C) Catamenia chart of colony germination assay. (D) Clonogenic survival of 1 time or two time BEMER therapy (~13 μT, 8 min) combined with six-Gy irradiation of indicated cell lines (BEMER sham-treated (sham), irradiated cells as command). All results represent mean ± SD. Student's t-test. due north = three. * P < 0.05; ** P < 0.01. northward.due south., not significant.

Fig half dozen. Sensitivity to chemotherapy and Cetuximab is not influenced past BEMER therapy.

(A) Menstruation chart of colony formation assay. Cells were plated in 3D lrECM, treated with corresponding agents followed past BEMER therapy 23 h subsequently. (B) Basal surviving fraction afterwards Cisplatin (0.ane μM; DMEM every bit control) treatment and BEMER therapy (~13 μT, 8 min). (C) Basal surviving fraction afterward Gemcitabine (10 nM; DMEM equally control) handling and BEMER therapy (~thirteen μT, 8 min). BEMER sham-treated (sham) cells served as control. (D) Basal surviving fraction afterwards Cetuximab (5 μg/ml; IgG equally control) treatment and BEMER therapy (~13 μT, 8 min). IgG-treated cells served as control. All results represent mean ± SD. Student's t-examination. north = 3. * P < 0.05; ** P < 0.01. due north.s., non significant.

Fig 7. BEMER therapy-mediated radiosensitization remains unaltered upon chemotherapy and Cetuximab.

(A) Flow chart of colony formation analysis. (B) Clonogenic survival later on half-dozen-Gy irradiation combined with BEMER therapy (~13 μT, viii min) and Cisplatin (0.1 μM; DMEM as control). (C) Clonogenic survival afterwards 6-Gy irradiation combined with BEMER therapy (~13 μT, 8 min) and Gemcitabine (ten nM; DMEM as control). Sham-treated (sham) simply irradiated cells served as control. (D) Clonogenic survival after 6-Gy irradiation combined with BEMER therapy (~13 μT, 8 min) and Cetuximab (5 μg/ml; IgG as control). IgG-treated, irradiated cells served as control. All results correspond hateful ± SD. Pupil's t-test. n = three. * P < 0.05; ** P < 0.01. northward.s., not meaning.

Fig 8. BEMER signal intensity determines radiosensitization and DSB numbers.

(A) Flow chart of colony formation analysis and foci assay. (B) Clonogenic survival later half dozen-Gy irradiation combined with BEMER therapy (2.7–35 μT; 8 min) of A549 and UTSCC15 cells. (C) Immunofluorescence images show nuclei with γH2AX/53BP1-positive foci later 6-Gy irradiation with (~13 or ~35 μT; 8 min) and without BEMER therapy in A549 cells. (D) Number of γH2AX/53BP1-positive DSBs 24 h subsequently irradiation in A549 and UTSCC15 cells. BEMER sham-treated (sham), irradiated cells served as command. All results represent mean ± SD. Pupil's t-exam. n = 3. * P < 0.05; ** P < 0.01.

Fig 9. BEMER therapy induces elevated ROS levels resulting in increased DSB numbers.

(A) Menstruation chart of colony formation assay and foci assay. (B) Surviving fraction of indicated cell lines treated with sodium pyruvate (10 μM), MnTBAP (50 μM) or Carboxy-PTIO (l μM) in combination with BEMER therapy and radiotherapy. (C) Number of γH2AX/53BP1-positive DSBs 24 h after irradiation in A549 and UTSCC15 cells. Cells were treated with indicated scavenger agents and BEMER therapy (~35 μT, viii min). BEMER sham-treated (sham), irradiated cells served as control. All results correspond hateful ± SD. Student'due south t-test. northward = three. ** P < 0.01. n.s., non significant.

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Grant support

The enquiry and authors were in part supported by the BEMER Int. AG (Principality of liechtenstein) and grants from the Deutsche Krebshilfe (108976 to N.C.), the European union (RADIATE; GA No. 642623 to N.C.) and the EFRE Europäische Fonds für regionale Entwicklung, Europa fördert Sachsen (100066308). This work was also supported in function past a grant from the German language Federal Ministry building of Educational activity and Inquiry (BMBF) to the German Center for Diabetes Enquiry (DZD eastward.Five.). The funders had no role in written report design, data drove and analysis, determination to publish, or preparation of the manuscript.

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Source: https://pubmed.ncbi.nlm.nih.gov/27959944/

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