Low intensity and frequency pulsed electromagnetic fields selectively impair breast cancer cell viability
Sara Crocetti, Christian Beyer, Grit Schade, Marcel Egli, Jürg Fröhlich, Alfredo Franco-Obregón, Sara Crocetti, Christian Beyer, Grit Schade, Marcel Egli, Jürg Fröhlich, Alfredo Franco-Obregón
Abstract
Introduction: A common drawback of many anticancer therapies is non-specificity in action of killing. We investigated the potential of ultra-low intensity and frequency pulsed electromagnetic fields (PEMFs) to kill breast cancer cells. Our criteria to accept this technology as a potentially valid therapeutic approach were: 1) cytotoxicity to breast cancer cells and; 2) that the designed fields proved innocuous to healthy cell classes that would be exposed to the PEMFs during clinical treatment.
Methods: MCF7 breast cancer cells and their normal counterparts, MCF10 cells, were exposed to PEMFs and cytotoxic indices measured in order to design PEMF paradigms that best kill breast cancer cells. The PEMF parameters tested were: 1) frequencies ranging from 20 to 50 Hz; 2) intensities ranging from 2 mT to 5 mT and; 3) exposure durations ranging from 30 to 90 minutes per day for up to three days to determine the optimum parameters for selective cancer cell killing.
Results: We observed a discrete window of vulnerability of MCF7 cells to PEMFs of 20 Hz frequency, 3 mT magnitude and exposure duration of 60 minutes per day. The cell damage accrued in response to PEMFs increased with time and gained significance after three days of consecutive daily exposure. By contrast, the PEMFs parameters determined to be most cytotoxic to breast cancer MCF-7 cells were not damaging to normal MCF-10 cells.
Conclusion: Based on our data it appears that PEMF-based anticancer strategies may represent a new therapeutic approach to treat breast cancer without affecting normal tissues in a manner that is non-invasive and can be potentially combined with existing anti-cancer treatments.
Conflict of interest statement
Competing Interests: One of the authors, Grit Shade, is an employee of Amphasys, the company that provided the authors with the prototype of the Impedance Flow Cytometer utilized to conduct some of the experiments in the manuscript. GS provided technical support only. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
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References
- Barbault A, Costa FP, Bottger B, Munden RF, Bomholt F, et al. (2009) Amplitude-modulated electromagnetic fields for the treatment of cancer: Discovery of tumor-specific frequencies and assessment of a novel therapeutic approach. J Exper Clin Cancer Res 28: 51–61.
- Blackman CF (2012) Treating cancer with amplitude-modulated electromagnetic fields: a potential paradigm shift, again? Br J Cancer 106: 241–2.
- Cameron IL, Sun LZ, Short N, Hardman WE, Williams CD (2005) Therapeutic Electromagnetic Field (TEMF) and gamma irradiation on human breast cancer xenograft growth, angiogenesis and metastasis. Cancer Cell Int 5: 23.
- Elson EI (2009) The little explored efficacy of magnetic fields in cancer treatment and postulation of the mechanism of action. Electromagn Biol Med 28: 275–82.
- Zimmerman JW, Pennison MJ, Brezovich I, Yi N, Yang CT, et al. (2012) Cancer cell proliferation is inhibited by specific modulation frequencies. Br J Cancer 106: 307–13.
- Repacholi MH, Greenebaum B (1999) Interaction of static and extremely low frequency electric and magnetic fields with living systems: health effects and research needs. Bioelectromagnetics 20: 133–60.
- World Health Organization: Electromagnetic fields and public health (2007) Exposure to extremely low frequency fields. Available: . Accessed 2012 Nov 12.
- Crocetti S, Piantelli F, Leonzio C (2011) Selective destabilization of tumor cells with pulsed electric and magnetic sequences: a preliminary report. Electromagn Biol Med 30: 128–35.
- Ruiz-Gómez MJ, Martínez-Morillo M (2005) Enhancement of the cell-killing effect of ultraviolet-C radiation by short-term exposure to a pulsed magnetic field. Int J Radiat Biol 81: 483–90.
- Yamaguchi S, Ogiue-Ikeda M, Sekino M, Ueno S (2006) Effects of pulsed magnetic stimulation on tumor development and immune functions in mice. Bioelectromagnetics 27: 64–72.
- Cheung K, Gawad S, Renaud P (2005) Impedance spectroscopy flow cytometry: on-chip label-free cell differentiation. Cytometry A 65A: 124–32.
- Cheung K, Di Berardino M, Schade-Kampmann G, Hebeisen M, Pierzchalski A, et al. (2010) Microfluidic impedance-based flow cytometry. Cytometry A 77A: 648–66.
- David F, Hebeisen M, Schade G, Franco-Lara E, Di Berardino M (2012) Viability and membrane potential analysis of Bacillus megaterium cells by impedance flow cytometry. Biotechnol Bioeng 109: 483–92.
- Pierzchalski A, Hebeisen M, Mittag A, Bocsi J, Di Berardino M, et al. (2012) Label-free hybridoma cell culture quality control by a chip-based impedance flow cytometer. Lab Chip 12: 4533–4543.
- Schade-Kampmann G, Huwiler A, Hebeisen M, Hessler T, Di Berardino M (2008) On-chip non-invasive and label-free cell discrimination by impedance spectroscopy. Cell Prolif 41: 830–40.
- Chin S, Hughes MP, Coley HM, Labeed FH (2006) Rapid assessment of early biophysical changes in K562 cells during apoptosis determined using dielectrophoresis. Int J Nanomedicine 1: 333–7.
- Labeed FH, Coley HM, Hughes MP (2006) Differences in the biophysical properties of membrane and cytoplasm of apoptotic cells revealed using dielectrophoresis. Biochim Biophys Acta 1760: 922–9.
- Sul AR, Park S, Suh H (2006) Effects of sinusoidal electromagnetic field on structure and function of different kind of cell lines. Yonsei Med J 46: 852–861.
- Focke F, Schuermann D, Kuster N, Schär P (2010) DNA fragmentation in human fibroblasts under extremely low frequency electromagnetic field exposure. Mutat Res 683: 74–83.
- Koh EK, Ryu BK, Jeong DY, Bang IS, Nam MH, et al. (2008) A 60-Hz sinusoidal magnetic field induces apoptosis of prostate cancer cells through reactive oxygen species. Int J Radiat Biol 84: 945–55.
- Radeva M, Berg H (2004) Differences in lethality between cancer cells and human lymphocytes caused by LF-electromagnetic fields. Bioelectromagnetics 25: 503–7.
- Zhivotosky B, Orrenius S (2001) Assessment of apoptosis and necrosis by DNA fragmentation and morphological criteria. Curr Protoc Cell Biol 18: 18.3–18.3.23.
- Du Plessis-Stoman D, du Preez J, van de Venter M (2011) Combination treatment with oxaliplatin and mangiferin causes increased apoptosis and downregulation of NFκB in cancer cell lines. Afr J Tradit Complement Altern Med 8: 177–84.
- Wang X, Becker FF, Gascoyne PR (2002) Membrane dielectric changes indicate induced apoptosis in HL-60 cells more sensitively than surface phosphatidylserine expression or DNA fragmentation. Biochim Biophys Acta 1564: 412–20.
- Mattson MP, Chan SL (2003) Calcium orchestrates apoptosis. Nat Cell Biol 5(12): 1041–3.
- Cho Y, Kim HS, Frazier AB, Chen ZG, Shin DM, Han A (2009) Whole Cell Impedance Analysis for Highly and Poorly Metastatic Cancer Cells. J microelectromech 18: 808–817.
- Opp D, Wafula B, Lim J, Huang E, Lo JC, et al. (2009) Use of electric cell-substrate impedance sensing to assess in vitro cytotoxicity. Biosens Bioelectron 24: 2625–9.
- Vermes I, Haanen C, Steffens-Nakken H, Reutelingsperger C (1995) A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. . J Immunol Methods 184(1): 39–51.
- Ebrahimi Nigjeh S, Yusoff FM, Mohamed Alitheen NB, Rasoli M, Keong YS, et al. (2013) Cytotoxic effect of ethanol extract of microalga, Chaetoceros calcitrans, and its mechanisms in inducing apoptosis in human breast cancer cell line. Biomed Res Int 2013: 783690.
- International Commission for Non-Ionizing Radiation Protection (1998) ICNIRP Guidelines for limiting exposure to time-varying electric, magnetic and electromagnetic fields (up to 300 GHZ). Health Physics 74: 494–522.
- Ivancsits S, Diem E, Jahn O, Rüdiger HW (2003) Intermittent extremely low frequency electromagnetic fields cause DNA damage in a dose-dependent way. Int Arch Occup Environ Health 76: 431–6.
- Putney JW, Bird GS (2008) Cytoplasmic calcium oscillations and store-operated calcium influx. J Physiol 586: 3055–9.
- Shapovalov G, Lehen'kyi V, Skryma R, Prevarskaya N (2011) TRP channels in cell survival and cell death in normal and transformed cells. Cell Calcium 50: 295–302.
- Haddad JB, Obolensky AG, Shinnick P (2007) The biologic effects and the therapeutic mechanism of action of electric and electromagnetic field stimulation on bone and cartilage: new findings and a review of earlier work. J Altern Complement Med 13: 485–90.
- Monteith GR, McAndrew D, Faddy HM, Roberts-Thomson SJ (2007) Calcium and cancer: targeting Ca2+ transport. Nat Rev Cancer 7: 519–30.
- Sergeev IN (2004) Calcium as a mediator of 1,25-dihydroxyvitamin D3-induced apoptosis. J Steroid Biochem Mol Biol 89-90: 419–25.
- Sergeev IN (2005) Calcium signaling in cancer and vitamin D. . J Steroid Biochem Mol Biol 97: 145–51.
- Khaled AR, Reynolds DA, Young HA, Thompson CB, Muegge K, et al. (2001) Interleukin-3 withdrawal induces an early increase in mitochondrial membrane potential unrelated to the Bcl-2 family. Roles of intracellular pH, ADP transport, and F(0)F(1)-ATPase. J Biol Chem 276: 6453–62.
- Kim JY, Yu SJ, Oh HJ, Lee JY, Kim Y, et al. (2011) Panaxydol induces apoptosis through an increased intracellular calcium level, activation of JNK and p38 MAPK and NADPH oxidase-dependent generation of reactive oxygen species. Apoptosis 16(4): 347–58.
Source: PubMed