Electromagnetic field investigation on different cancer cell lines

BackgroundThere is a strong interest in the investigation of extremely low frequency Electromagnetic Fields (EMF) in the clinic. While evidence about anticancer effects exists, the mechanism explaining this effect is still unknown.MethodsWe investigated in vitro, and with computer simulation, the influence of a 50 Hz EMF on three cancer cell lines: breast cancer MDA-MB-231, and colon cancer SW-480 and HCT-116. After 24 h preincubation, cells were exposed to 50 Hz extremely low frequency (ELF) radiofrequency EMF using in vitro exposure systems for 24 and 72 h. A computer reaction-diffusion model with the net rate of cell proliferation and effect of EMF in time was developed. The fitting procedure for estimation of the computer model parameters was implemented.ResultsExperimental results clearly showed disintegration of cells treated with a 50 Hz EMF, compared to untreated control cells. A large percentage of treated cells resulted in increased early apoptosis after 24 h and 72 h, compared to the controls. Computer model have shown good comparison with experimental data.ConclusionUsing EMF at specific frequencies may represent a new approach in controlling the growth of cancer cells, while computer modelling could be used to predict such effects and make optimisation for complex experimental design. Further studies are required before testing this approach in humans.

[1]  C. Rinehart,et al.  Selective potentiation of gynecologic cancer cell growth in vitro by electromagnetic fields. , 1998, Gynecologic oncology.

[2]  U. Zimmermann,et al.  Rotation of Cells in an Alternating Electric Field: the Occurrence of a Resonance Frequency , 1981, Zeitschrift fur Naturforschung. Section C, Biosciences.

[3]  N. Arsenijević,et al.  Analysis of cycloheximide‐induced apoptosis in human leukocytes: Fluorescence microscopy using annexin V/propidium iodide versus acridin orange/ethidium bromide , 2006, Cell biology international.

[4]  Luzhe Sun,et al.  Therapeutic Electromagnetic Field (TEMF) and gamma irradiation on human breast cancer xenograft growth, angiogenesis and metastasis , 2005, Cancer Cell International.

[5]  John H. Holland,et al.  Adaptation in Natural and Artificial Systems: An Introductory Analysis with Applications to Biology, Control, and Artificial Intelligence , 1992 .

[6]  Niels Kuster,et al.  Amplitude-modulated electromagnetic fields for the treatment of cancer: Discovery of tumor-specific frequencies and assessment of a novel therapeutic approach , 2009, Journal of experimental & clinical cancer research : CR.

[7]  C. Oliveira,et al.  Apoptosis as a mechanism of cell death induced by different chemotherapeutic drugs in human leukemic T-lymphocytes☆ , 1996 .

[8]  S. Xue,et al.  Role of calcium in apoptosis of HL-60 cells induced by harringtonine , 1998, Science in China Series C: Life Sciences.

[9]  N. Kuster,et al.  Treatment of advanced hepatocellular carcinoma with very low levels of amplitude-modulated electromagnetic fields , 2011, British Journal of Cancer.

[10]  E. Kirson,et al.  A Pilot Study with Very Low-Intensity, Intermediate-Frequency Electric Fields in Patients with Locally Advanced and/or Metastatic Solid Tumors , 2008, Oncology Research and Treatment.

[11]  Charles Polk,et al.  Therapeutic Applications of Low-Frequency Sinusoidal and Pulsed Electric and Magnetic Fields , 1999 .

[12]  J. Marcinkiewicz,et al.  Pulsating electromagnetic field stimulation prevents cell death of puromycin treated U937 cell line. , 2010, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[13]  E. Kirson,et al.  TTFields alone and in combination with chemotherapeutic agents effectively reduce the viability of MDR cell sub-lines that over-express ABC transporters , 2010, BMC Cancer.

[14]  P. D. de Lima,et al.  Apoptosis as a mechanism of cell death induced by different chemotherapeutic drugs in human leukemic T-lymphocytes. , 1996, Biochemical pharmacology.

[15]  E. Kirson,et al.  Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs , 2009, Clinical & Experimental Metastasis.

[16]  K. Tachibana,et al.  Bio-effects of non-ionizing electromagnetic fields in context of cancer therapy. , 2014, Frontiers in bioscience.

[17]  J. Lamb,et al.  Different glycosylation of cadherins from human bladder non-malignant and cancer cell lines , 2002, Cancer Cell International.

[18]  J. Murray,et al.  A mathematical model of glioma growth: the effect of chemotherapy on spatio‐temporal growth , 1995, Cell proliferation.

[19]  D. Absher,et al.  Cancer cell proliferation is inhibited by specific modulation frequencies , 2011, British Journal of Cancer.

[20]  N. Olea,et al.  Could radiotherapy effectiveness be enhanced by electromagnetic field treatment? , 2013, International journal of molecular sciences.

[21]  C. Bassett,et al.  The development and application of pulsed electromagnetic fields (PEMFs) for ununited fractures and arthrodeses. , 1985, Clinics in plastic surgery.

[22]  J. Murray,et al.  A mathematical model of glioma growth: the effect of extent of surgical resection , 1996, Cell proliferation.

[23]  K. Swanson,et al.  A mathematical model for brain tumor response to radiation therapy , 2009, Journal of mathematical biology.

[24]  J. Vienken,et al.  Rotation of cells in an alternating electric field theory and experimental proof , 2005, The Journal of Membrane Biology.

[25]  Joseph D. Bronzino,et al.  The Biomedical Engineering Handbook , 1995 .

[26]  L. Ji.  Radiofrequency hyperthermia in combination with internvention chemotherapy in the treatment of advanced colorectal cancer , 2006 .

[27]  Nenad D Filipovic,et al.  Transient finite element modeling of functional electrical stimulation. , 2011, General physiology and biophysics.

[28]  E. Dekel,et al.  Disruption of cancer cell replication by alternating electric fields. , 2004, Cancer research.

[29]  P. Marszalek,et al.  Bioelectrorheological model of the cell. 5. Electrodestruction of cellular membrane in alternating electric field. , 1993, Biophysical journal.

[30]  P. Gutin,et al.  NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. , 2012, European journal of cancer.

[31]  Husheng Zhang,et al.  EXTREMELY LOW FREQUENCY (ELF) PULSED‐GRADIENT MAGNETIC FIELDS INHIBIT MALIGNANT TUMOUR GROWTH AT DIFFERENT BIOLOGICAL LEVELS , 2002, Cell biology international.

[32]  Salvatore Torquato,et al.  Simulating tumor growth in confined heterogeneous environments , 2008, Physical biology.

[33]  John A. Nelder,et al.  A Simplex Method for Function Minimization , 1965, Comput. J..

[34]  J. Murray,et al.  Virtual and real brain tumors: using mathematical modeling to quantify glioma growth and invasion , 2003, Journal of the Neurological Sciences.

[35]  J. Vymazal,et al.  Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields) , 2009, BMC medical physics.

[36]  E. Dekel,et al.  Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors , 2007, Proceedings of the National Academy of Sciences.

[37]  Yanyu Liu,et al.  Chiral Ruthenium(II) Polypyridyl Complexes: Stabilization of G-Quadruplex DNA, Inhibition of Telomerase Activity and Cellular Uptake , 2012, PloS one.

[38]  T. Mosmann.  Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[39]  A. Barbault,et al.  Targeted treatment of cancer with radiofrequency electromagnetic fields amplitude-modulated at tumor-specific frequencies , 2013, Chinese journal of cancer.

[40]  Y. Palti.  Stimulation of internal organs by means of externally applied electrodes. , 1966, Journal of applied physiology.

[41]  E. Elson,et al.  Biologic Effects of Radiofrequency and Microwave Fields: In Vivo and In Vitro Experimental Results , 1999 .