Nanosecond Pulsed Electric Fields (nsPEFs) Induce Socs1 and Socs3 but not Socs2 Gene Expressions in Hela S3 Cells
DOI:
https://doi.org/10.21776/ub.jkb.2015.028.03.1Abstract
Nanosecond Pulsed Electric Fields (nsPEFs) is one of bioelectric technologies applied widely in a number of sciences. nsPEFs cause some biological responses and known to play a role as a novel cancer therapy. However, the nsPEFs molecular mechanisms have not been fully elucidated. This study determines the effects of nsPEFs in socs (Suppressor of Cytokine Signaling) genes which are target genes of JAK/STAT signaling pathway. Through a negative feedback mechanism, SOCS proteins can suppress both cytokine signal transduction and overgrowth factor, so the cell growth is controlled. In cervix cancer, the presence of E6 and E7 HPV's oncoprotein is associated with methylation and inactivation of socs1 and socs3 genes. This mechanism is related to the increase of STAT expression and cancer prognostic. In this research, nsPEFs as much as 20 kV/cm for 80 ns was exposed over HeLa S3 cells in 4 mm cuvette. Socs1, socs2 and socs3 gene expressions were analyzed using real time PCR SYBR green and reverse transcription PCR (RT-PCR). This study shows that at 20 and 30 shots, nsPEFs significantly increase socs1 and socs3 but not socs2 gene expression. Effect of nsPEFs on socs1 and socs3 gene expression pattern is influenced by duration of post exposure incubation and each cell activity on internal cell condition. This research provides a new cancer therapy target for nsPEFs.
Keywords: Bioelectric, gene expression, nsPEFs, shot, socs gene
Downloads
References
Chen C, Smye SW, Robinson MP, and Evan JA. Membrane Electroporation Theories: A Review. Medical & Biological Engineering & Computing. 2006; 44(1-2): 5-14.
Beebe SJ and Schoenbach KH. Nanosecond Pulsed Electric Fields: A New Stimulus to Activate Intracellular Signaling. Journal of Biomedicine and Biotechnology. 2005; 2005(4): 297-300.
Deng J, Schoenbach KH, Buescher ES, Hair P, Fox PM, and Beebe SJ. The Effect of Intense Submicrosecond Electrical Pulses on cells. Biophysical Journal. 2003; 84(4): 2709-2714.
Crasivo GL, Choe S, Chatterjee P, Chatterjee I, and Vernier PT. Nanosecond Electric Pulses: A Novel Stimulus for Triggering Ca2+ Influx into Chromaffin Cells Via Voltage-Gated Ca2+ Channels. Cellular and Molecular Neurobiology. 2010; 30(8): 1259-1265.
Weaver JC, Smith KC, Esser AT, Son RS, and Gowrishanker TR. A Brief Overview of Electroporation Pulse Strength-Duration Space: A Region Where Additional Intracellular Effects are expected. Bioelectrochemistry. 2012; 87: 236-243.
Napotnik TB, Wu Y, Gundersen MA, Miklavcic D, and Vernier PT. Nanosecond Electric Pulses Cause Mitochondrial Membrane Permeabilization in Jurkat Cells. Bioelectromagnetic. 2012; 33(3): 257-264.
Beebe SJ, Sain NM, and Ren W. Induction of Cell Death Mechanisms and Apoptosis by Nanosecond Pulsed Electric Fields (nsPEFs). Cells. 2013; 2(1): 136-162.
Beebe SJ, Chen YJ, Sain NM, Soenbach KH, and Xiao, S. Transient Feature in Nanosecond Pulsed Electric Fields Differentially Modulate Mitochondria and Viability. PLoS One. 2012;7(12): e51349
Vernier PT, Sun Y, Mercu L, Salemi S, Craft SM, and Gundersen MA. Calcium Bursts Induced by Nanosecond Electric Pulses. Biochemical and Biophysical Research Communications. 2003; 310(2): 286-295.
Morotomi-Yano K, Akiyama H, and Yano K. Nanosecond Pulsed Electric Fields Activate MAPK Pathways in Human Cells. Biochemical and Biophysical Research Communications. 2011; 515(1-2): 99-106.
Morotomi-Yano K, Akiyama H, and Yano K. Nanosecond Pulsed Electric Fields Activate AMP-Activated Protein Kinase: Implications for Calcium-Mediated Activation of Cellular Signaling. Biochemical and Biophysical Research Communications. 2012; 428(3): 371-375.
Ren Z, Chen X, Cui G, et al. Nanosecond Pulsed Electric Field Inhibits cancer Growth Followed by Alteration in Expression of NF-kB and Wnt/β-catenin Signaling Molecules. PLoS One. 2013; 8(9): e74322.
Morotomi-Yano K, Oyadomari S, Akiyama H, and Yano K. Nanosecond Pulsed Electric Act as a Novel Cellular Stress That Induces Translational Suppression Accompanied by elF2a Phosphorylation and 4E-BP1 Dephosphorylation. Experimental Cell Research. 2012; 318: 1733-1744.
Beebe SJ, Blackmore PF, White J, Joshi RP, and Schoenbach KH. Nanosecond Pulsed Electric Fields Modulate Cell Function through Intracellular Signal Transduction Mechanisms. Physiologica Measurement. 2004; 25(4): 1077-1093.
Stacey M, Fox P, Buescher S, and Kolb J. Nanosecond Pulsed Electric Field Induced Cytoskeleton, Nuclear Membrane and Telomere Damage Adversely Impact Cell Survical. Bioelectrochemistry. 2011; 82(2): 131-134.
Beebe SJ, Fox PM, Rec LJ, Willis LK, and Schoenbach KH. Nanosecond, High-Intensity Pulsed Electric Fields Induce Apoptosis in Human Cell. The Journal of the Federation of American Societies for Experimental Biology. 2003; 17(11): 1493-1495.
Ren W and Beebe SJ. An Apoptosis Targeted Stimulus with Nanosecond Pulsed Electric Fields (NsPEFs) in E4 Squamous Cell Carcinoma. Apoptosis. 2011; 16(4): 382-393.
Ford WE, Ren W, Blackmore PF, Schoenback KH, and Beebe SJ. Nanosecond Pulsed Electric Fields Stimulate Apoptosis without Release of Pro-Apoptototic Factors from Mitochondria in B16f10 Melanoma. Archieves of Bioechemistry and Biophysics. 2010; 497(1-2): 82-89.
Stacey M, Stickley J, Fox P, et al. Differential Effects in Cells Exposed to Ultra-Short, High Intensity Electric Fields: Cell Survival, DNA Damage, and Cell Cycle Analysis. Mutation Research. 2003; 542(1-2): 65-75.
Nagahama M, Shimomura N, Nakagawa A, Teranishi K, Uto Y, and Hori H. In Vivo Experimental Study of Nanosecond Pulsed Electric Field Effects on Solid Tumors. IEEE Transactions on Dielectrics and Electrical Insulation. 2013; 20(4): 1266-1272.
Nuccitelli R, Pliquett U, Chen X, et al. Nanosecond Pulsed Electric Fields Cause Melanomas to Self-Destruct. Biochemical and Biophysical Research Communications. 2006; 343(2): 351-360.
Wu S, Wang Y, Guo J, Chen Q, Zhang J, and Fang J. Nanosecond Pulsed Electric fields as a Novel Drug Free Therapy for Breast Cancer: An In Vivo Study. Cancer Letters. 2014; 343(2): 268-274.
Beebe SJ. Bioelectrics in Basic Science and Medicine: Impact of Electric Fields on Cellular Structures and Functions. Nanomedicine and Nanotechnology. 2013; 4(2): 1-8.
Rawlings JS, Rosler KM, and Horrison DA. The JAK/STAT Signaling Pathway. Journal of Cell Science. 2004; 117: 1281-1283.
Elliott J, Hookham MB, and Johnston JA. The Suppressors of Cytokine Signalling E3 Ligases Behaves as Tumor Suppressors. Biochemical Society Transactions. 2008; 36(Pt3): 464-468.
Weniger MA, Melzner I, Menz CK, et al. Mutations of the Tumor Suppressor Gene SOCS1 in Classical Hodgkin Lymphoma are Frequent and Associated with Nuclear Phospho-STAT5 Accumulation. Oncogene. 2006; 25(18): 2679–2684.
Nagai H, Naka T, Terada Y, et al. Hypermethylation Associated with Inactivation of the SOCS-1 Gene, a JAK/STAT Inhibitor, in Human Hepatoblastomas. Journal of Human Genetics. 2003; 48(2): 65-69.
Downloads
Published
Issue
Section
License
Authors who publish with this journal agree to the following terms:- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).