Alternating Electric Fields (TTFields) Activate Cav1.2 Channels in Human Glioblastoma Cells
Open accessAbstract
Tumor treating fields (TTFields) represent a novel FDA-approved treatment modality for patients with newly diagnosed or recurrent glioblastoma multiforme. This therapy applies intermediate frequency alternating electric fields with low intensity to the tumor volume by the use of non-invasive transducer electrode arrays. Mechanistically, TTFields have been proposed to impair formation of the mitotic spindle apparatus and cytokinesis. In order to identify further potential molecular targets, here the effects of TTFields on Ca2+-signaling, ion channel activity in the plasma membrane, cell cycle, cell death, and clonogenic survival were tested in two human glioblastoma cell lines in vitro by fura-2 Ca2+ imaging, patch-clamp cell-attached recordings, flow cytometry and pre-plated colony formation assay. In addition, the expression of voltage-gated Ca2+ (Cav) channels was determined by real-time RT-PCR and their significance for the cellular TTFields response defined by knock-down and pharmacological blockade. As a result, TTFields stimulated in a cell line-dependent manner a Cav1.2-mediated Ca2+ entry, G1 or S phase cell cycle arrest, breakdown of the inner mitochondrial membrane potential and DNA degradation, and/or decline of clonogenic survival suggesting a tumoricidal action of TTFields. Moreover, inhibition of Cav1.2 by benidipine aggravated in one glioblastoma line the TTFields effects suggesting that Cav1.2-triggered signaling contributes to cellular TTFields stress response. In conclusion, the present study identified Cav1.2 channels as TTFields target in the plasma membrane and provides the rationale to combine TTFields therapy with Ca2+ antagonists that are already in clinical use.
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In Neuhaus et al., anti-clonogenicity was significant but low at 10% after 5-7 days.
“They noted that anti-clonogenicity was significant but low at 10% after 5–7 days [46].”
From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [46]
Neuhaus et al. showed correlation of AEF effects on Cav1.2 channels with previously reported TTFields effects, but not causation.
“In summary, Neuhaus et al. showed correlation of AEF effects on Cav1.2 channels with previously reported TTFields’ effects, but not causation, probably due to low AEF field strength and use of a single-direction electric field [46].”
From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [46]
The low efficacy in Neuhaus et al. is probably due to the lower field strength (1 V/cm) compared to the 2-3 V/cm needed for higher efficacy, and to the use of a single-direction electric field.
“The low efficacy is probably due to the lower field strength (1 V/cm in Neuhaus et al. [46]) compared to what Kirson et al. [47] showed is needed for higher efficacy: 2–3 V/cm [47]. The latter setting resulted in a reduction in cancer cell number [47]. Neuhaus et al. also did not change the AEF direction with respect to the cells, which significantly increases efficacy as demonstrated by Kirson et”
From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [46]
200 kHz AEFs at 1 V/cm (TTFields) affected a voltage-gated calcium channel (Cav1.2) in T98 human glioblastoma cells and produced apoptosis as well as G1 or S phase cell cycle arrest, breakdown of the inner mitochondrial membrane potential, and DNA degradation.
“For example, using several empirical techniques, Neuhaus et al. [46] showed that 200 kHz AEFs at 1 V/cm (i.e., TTFields) affected a voltage-gated calcium channel (Cav1.2) in T98 human glioblastoma cells and produced apoptosis as well as G1 or S phase cell cycle arrest, breakdown of the inner mitochondrial membrane potential, and DNA degradation [46].”
From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [46]
Ion channel activation and ion influx, and perhaps other effects such as cytoskeleton damage, can be used as biomarkers of responsiveness to TTFields.
“The results from electroporation studies further support that ion channel activation and ion influx, and perhaps other effects such as cytoskeleton damage, can be used as biomarkers of responsiveness to TTFields, given that these phenomena are observed after exposure to electric fields [27,46,62,65].”
From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [46]
Calcium influx and Cav2+ activation might serve as novel biomarkers of the efficacy of TTFields.
“Calcium influx and Cav2+ activation might also serve as novel biomarkers of the efficacy of TTFields [46].”
From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [46]
TTFields have been reported to activate Cav2+ channels.
“For example, TTFields have been reported to activate Cav2+ channels [46], membrane distortions predicted by the bioelectrorheological model are likely another feature of TTFields’ actions [40], and membrane fenestration is a hallmark of reversible electroporation [62].”
From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [46]
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Cites
Cerami, E., Gao, J., Dogrusoz, U., Gross, B. E., Sumer, S. O., Aksoy, B. A., Jacobsen, A., Byrne, C. J., Heuer, M. L., Larsson, E., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0095 · Cited by 17,455 · see citing works
Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal
Gao, J., Aksoy, B. A., Dogrusoz, U., Dresdner, G., Gross, B., Sumer, S. O., Sun, Y., Jacobsen, A., Sinha, R., Larsson, E., et al. (2013) · Science Signaling · doi:10.1126/scisignal.2004088 · Cited by 15,160 · see citing works
Calcium's Role in Mechanotransduction during Muscle Development
Damm, T. B., & Egli, M. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000356667 · Cited by 14,548 · see citing works
Stupp, R., Taillibert, S., Kanner, A., Read, W., Steinberg, D. M., Lhermitte, B., Toms, S., Idbaih, A., Ahluwalia, M. S., Fink, K., et al. (2017) · JAMA · doi:10.1001/jama.2017.18718 · Cited by 2,644 · see citing works
Zamponi, G., Striessnig, J., Koschak, A., & Dolphin, A. (2015) · Pharmacological Reviews · doi:10.1124/pr.114.009654 · Cited by 1,004 · see citing works
Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors
Kirson, E. D., Dbalý, V., Tovaryš, F., Vymazal, J., Soustiel, J. F., Itzhaki, A., Mordechovich, D., Steinberg-Shapira, S., Gurvich, Z., Schneiderman, R., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702916104 · Cited by 894 · see citing works
Stupp, R., Wong, E. T., Kanner, A. A., Steinberg, D., Engelhard, H., Heidecke, V., Kirson, E. D., Taillibert, S., Liebermann, F., Dbalý, V., et al. (2012) · European Journal of Cancer · doi:10.1016/j.ejca.2012.04.011 · Cited by 862 · see citing works
Disruption of cancer cell replication by alternating electric fields
Kirson, E. D., Gurvich, Z., Schneiderman, R., Dekel, E., Itzhaki, A., Wasserman, Y., Schatzberger, R., & Palti, Y. (2004) · Cancer research · doi:10.1158/0008-5472.can-04-0083 · Cited by 827 · see citing works
Stupp, R., Taillibert, S., Kanner, A. A., Read, W. L., Steinberg, D. M., Lhermitte, B., Toms, S. A., Idbaïh, A., Ahluwalia, M. S., Fink, K., et al. (2017) · Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) · doi:10.5167/uzh-143757 · Cited by 630 · see citing works
The current and potential role of hyperthermia in radiotherapy
Overgaard, J. (1989) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(89)90470-7 · Cited by 507 · see citing works
Pall, M. L. (2013) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12088 · Cited by 440 · see citing works
Giladi, M., Schneiderman, R. S., Voloshin, T., Porat, Y., Munster, M., Blat, R., Sherbo, S., Bomzon, Z., Urman, N., Itzhaki, A., et al. (2015) · Scientific Reports · doi:10.1038/srep18046 · Cited by 327 · see citing works
Piacentini, R., Ripoli, C., Mezzogori, D., Azzena, G. B., & Grassi, C. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21293 · Cited by 252 · see citing works
Kirson, E. D., Schneiderman, R. S., Dbalý, V., Tovaryš, F., Vymazal, J., Itzhaki, A., Mordechovich, D., Gurvich, Z., Shmueli, E., Goldsher, D., et al. (2009) · BMC Medical Physics · doi:10.1186/1756-6649-9-1 · Cited by 224 · see citing works
Grassi, C., D’Ascenzo, M., Torsello, A., Martinotti, G., Wolf, F. I., Cittadini, A. R. M., & Azzena, G. B. (2003) · Cell Calcium · doi:10.1016/j.ceca.2003.09.001 · Cited by 224 · see citing works
Tumor Treating Fields Perturb the Localization of Septins and Cause Aberrant Mitotic Exit
Gera, N., Yang, A., Holtzman, T. S., Lee, S. X., Wong, E. T., & Swanson, K. D. (2015) · PLOS ONE · doi:10.1371/journal.pone.0125269 · Cited by 217 · see citing works
Constitutively active L-type Ca 2+ channels
Navedo, M. F., Amberg, G. C., Votaw, V. S., & Santana, L. F. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500360102 · Cited by 203 · see citing works
Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs
Kirson, E. D., Giladi, M., Gurvich, Z., Itzhaki, A., Mordechovich, D., Schneiderman, R. S., Wasserman, Y., Ryffel, B., Goldsher, D., & Palti, Y. (2009) · Clinical & Experimental Metastasis · doi:10.1007/s10585-009-9262-y · Cited by 171 · see citing works
Broadband dielectric spectroscopy on human blood
Wolf, M., Gulich, R., Lunkenheimer, P., & Loidl, A. (2011) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.05.012 · Cited by 162 · see citing works
Giladi, M., Munster, M., Schneiderman, R. S., Voloshin, T., Porat, Y., Blat, R., Zielinska-Chomej, K., Hååg, P., Bomzon, Z., Kirson, E. D., et al. (2017) · Radiation Oncology · doi:10.1186/s13014-017-0941-6 · Cited by 159 · see citing works
Wong, E. T., Lok, E., Gautam, S., & Swanson, K. D. (2015) · British Journal of Cancer · doi:10.1038/bjc.2015.238 · Cited by 152 · see citing works
Pall, M. L. (2015) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2015.08.001 · Cited by 145 · see citing works
Karanam, N. K., Kalayarasan, S., Ding, L., Sishc, B. J., Saha, D., & Story, M. D. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.136 · Cited by 136 · see citing works
Giladi, M., Weinberg, U., Schneiderman, R. S., Porat, Y., Munster, M., Voloshin, T., Blatt, R., Cahal, S., Itzhaki, A., Onn, A., et al. (2014) · Seminars in Oncology · doi:10.1053/j.seminoncol.2014.09.006 · Cited by 132 · see citing works
Molecular basis of ancestral vertebrate electroreception
Bellono, N. W., Leitch, D. B., & Julius, D. J. (2017) · Nature · doi:10.1038/nature21401 · Cited by 127 · see citing works
Zhang, Y., Zhang, J., Jiang, D., Zhang, D., Qian, Z., Liu, C., & Tao, J. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.01852.x · Cited by 119 · see citing works
Lacouture, M. E., Davis, M. E., Elzinga, G., Butowski, N. A., Tran, D. D., Villano, J. L., DiMeglio, L., Davies, A. M., & Wong, E. T. (2014) · Seminars in Oncology · doi:10.1053/j.seminoncol.2014.03.011 · Cited by 111 · see citing works
Biological activity of tumor-treating fields in preclinical glioma models
Silginer, M., Weller, M., Stupp, R., & Roth, P. (2017) · Cell Death & Disease · doi:10.1038/cddis.2017.171 · Cited by 111 · see citing works
Pless, M., Droege, C., von Moos, R., Salzberg, M. O., & Betticher, D. C. (2013) · Lung Cancer · doi:10.1016/j.lungcan.2013.06.025 · Cited by 108 · see citing works
Giladi, M., Schneiderman, R. S., Porat, Y., Munster, M., Itzhaki, A., Mordechovich, D., Cahal, S., Kirson, E. D., Weinberg, U., & Palti, Y. (2014) · Pancreatology · doi:10.1016/j.pan.2013.11.009 · Cited by 98 · see citing works
Yao, K., Nagashima, K., & Miki, H. (2006) · Journal of Pharmacological Sciences · doi:10.1254/jphs.dtj05001x · Cited by 97 · see citing works
Zhang, X. (2012) · Oncology Reports · doi:10.3892/or.2012.1715 · Cited by 95 · see citing works
Ionizing radiation induces migration of glioblastoma cells by activating BK K+ channels
Steinle, M., Palme, D., Misovic, M., Rudner, J., Dittmann, K., Łukowski, R., Ruth, P., & Huber, S. M. (2011) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2011.05.069 · Cited by 95 · see citing works
Self-citationMorgado‐Valle, C., Verdugo‐Díaz, L., Garcı́a, D. E., Morales-Orozco, C., & Drucker-Colı́n, R. (1998) · Cell and Tissue Research · doi:10.1007/s004410050992 · Cited by 94 · see citing works
Enhanced MGMT expression contributes to temozolomide resistance in glioma stem-like cells
Qiu, Z.-K., Shen, D., Chen, Y.-S., Yang, Q.-Y., Guo, C.-C., Feng, B.-H., & Chen, Z. P. (2013) · 癌症：英文版 · doi:10.5732/cjc.012.10236 · Cited by 78 · see citing works
Vergote, I. B., von Moos, R., Manso, L., Nieuwenhuysen, E. V., Concin, N., & Sessa, C. (2018) · Gynecologic Oncology · doi:10.1016/j.ygyno.2018.07.018 · Cited by 78 · see citing works
Voloshin, T., Munster, M., Blatt, R., Shteingauz, A., Roberts, P. C., Schmelz, E. M., Giladi, M., Schneiderman, R. S., Zeevi, E., Porat, Y., et al. (2016) · International Journal of Cancer · doi:10.1002/ijc.30406 · Cited by 77 · see citing works
Salzberg, M., Kirson, E., Palti, Y., & Rochlitz, C. (2008) · Onkologie · doi:10.1159/000137713 · Cited by 68 · see citing works
Li, Y., Yan, X., Liu, J., Li, L., Hu, X., Sun, H., & Tian, J. (2014) · Neurochemistry International · doi:10.1016/j.neuint.2014.06.004 · Cited by 67 · see citing works
Schneiderman, R. S., Shmueli, E., Kirson, E. D., & Palti, Y. (2010) · BMC Cancer · doi:10.1186/1471-2407-10-229 · Cited by 65 · see citing works
Porat, Y., Giladi, M., Schneiderman, R. S., Blat, R., Shteingauz, A., Zeevi, E., Munster, M., Voloshin, T., Kaynan, N., Tal, O., et al. (2017) · Journal of Visualized Experiments · doi:10.3791/55820 · Cited by 65 · see citing works
BK K+ channel blockade inhibits radiation-induced migration/brain infiltration of glioblastoma cells
Edalat, L., Stegen, B., Klumpp, L., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.7423 · Cited by 64 · see citing works
Self-citationKessler, A. F., Frömbling, G. E., Gross, F., Hahn, M., Dzokou, W., Ernestus, R.-I., Löhr, M., & Hagemann, C. (2018) · Cell Death Discovery · doi:10.1038/s41420-018-0079-9 · Cited by 64 · see citing works
KCa3.1 Channels and Glioblastoma: In Vitro Studies
Klumpp, L., Sezgın, E., Skardelly, M., et al. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170808115821 · Cited by 61 · see citing works
Self-citationBurke, R. C., Bardet, S. M., Carr, L., Romanenko, S., Arnaud-Cormos, D., Leveque, P., & O'Connor, R. P. (2017) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2017.07.004 · Cited by 58 · see citing works
Ca2+-Activated IK K+ Channel Blockade Radiosensitizes Glioblastoma Cells
Stegen, B., Butz, L., Klumpp, L., et al. (2015) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-15-0075 · Cited by 57 · see citing works
Self-citationRosa, P., Catacuzzeno, L., Sforna, L., et al. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.26448 · Cited by 56 · see citing works
Catacuzzeno, L., & Franciolini, F. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19102970 · Cited by 55 · see citing works
Pall, M. L. (2015) · Reviews on Environmental Health · doi:10.1515/reveh-2015-0001 · Cited by 54 · see citing works
Gutin, P. H., & Wong, E. T. (2012) · American Society of Clinical Oncology Educational Book · doi:10.14694/edbook_am.2012.32.122 · Cited by 54 · see citing works
Larkin, J. G., Thompson, G., Scobie, G., Forrest, G., Drennan, J. E., & Brodie, M. J. (1992) · Epilepsia · doi:10.1111/j.1528-1157.1992.tb02358.x · Cited by 50 · see citing works
Electrical stimulation towards melanoma therapy via liquid metal printed electronics on skin
Li, J., Guo, C., Wang, Z., Gao, K., Shi, X., & Liu, J. (2016) · Clinical and Translational Medicine · doi:10.1186/s40169-016-0102-9 · Cited by 46 · see citing works
Clark, P. A., Gaal, J. T., Strebe, J. K., Pasch, C. A., Deming, D. A., Kuo, J. S., & Robins, H. I. (2016) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2016.10.042 · Cited by 46 · see citing works
Enhanced MGMT expression contributes to temozolomide resistance in glioma stem-like cells
Zhi-Kun, Qiu, Dong, et al. (2014) · 癌症：英文版 · Cited by 43 · see citing works
TRPM8 is required for survival and radioresistance of glioblastoma cells
Klumpp, D., Frank, S. C., Klumpp, L., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.21436 · Cited by 41 · see citing works
Self-citationKim, J. H., Sohn, U. D., Kim, H., & Kim, H. R. (2018) · Korean Journal of Physiology and Pharmacology · doi:10.4196/kjpp.2018.22.3.277 · Cited by 38 · see citing works
Luo, F., Yang, N., He, C., Li, H., Li, C., Chen, F., Xiong, J., Hu, Z., & Zhang, J. (2014) · Environmental Research · doi:10.1016/j.envres.2014.09.023 · Cited by 31 · see citing works
K+ channel signaling in irradiated tumor cells
Stegen, B., Klumpp, L., Misovic, M., Edalat, L., Eckert, M., Klumpp, D., Ruth, P., & Huber, S. M. (2016) · European Biophysics Journal · doi:10.1007/s00249-016-1136-z · Cited by 30 · see citing works
Self-citationCellular Effects of the Antiepileptic Drug Valproic Acid in Glioblastoma
Eckert, M., Klumpp, L., & Huber, S. M. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000485753 · Cited by 29 · see citing works
Self-citationCatacuzzeno, L., Caramia, M., Sforna, L., et al. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00152 · Cited by 27 · see citing works
Meletath, S. K., Pavlick, D. C., Brennan, T. J., Hamilton, R. H., Chmielecki, J., Elvin, J. A., Palma, N. A., Ross, J. S., Miller, V. A., Stephens, P. J., et al. (2016) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2016.0145 · Cited by 27 · see citing works
Porat, Y., Giladi, M., Schneiderman, R. S., Blat, R., Shteingauz, A., Zeevi, E., Munster, M., Voloshin, T., Kaynan, N., Tal, O., et al. (2017) · Journal of Visualized Experiments · doi:10.3791/55820-v · Cited by 25 · see citing works
Park, S. Y., Shim, J. H., Kim, M. K., et al. (2010) · Korean Journal of Physiology and Pharmacology · doi:10.4196/kjpp.2010.14.1.29 · Cited by 13 · see citing works
Tumor growth delay by adjuvant alternating electric fields which appears non-thermally mediated
Castellví, Q., Morell, M., Capellá, G., & Ivorra, A. (2015) · Bioelectrochemistry · doi:10.1016/j.bioelechem.2015.04.006 · Cited by 11 · see citing works
Kobayashi, H., Ohishi, T., NISHIIE, H., et al. (1988) · PubMed · Cited by 5 · see citing works
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Permeabilizing Cell Membranes with Electric Fields
Aguilar, A. A., Ho, M. C., Chang, E., Carlson, K. W., Natarajan, A., Marciano, T., Bomzon, Z., & Patel, C. B. (2021) · Cancers · doi:10.3390/cancers13092283 · Cited by 76 · see citing works
Li, X., Yang, F., & Rubinsky, B. (2020) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2020.2965883 · Cited by 59 · see citing works
- Authors
- Neuhaus, E., Zirjacks, L., Ganser, K., Klumpp, L., Schüler, U., Zips, D., Eckert, F., & Huber, S. M.
- Affiliations
- University of Tübingen (DE)
- German Cancer Research Center (DE)
- Corresponding author
- Huber, Stephan M.
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2019-01-18
- Volume
- 11
- Issue
- 1
- Pages
- 110
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC6356873
- OpenAlex
- W2909570965
- Cited by
- 63
- References
- 65
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 7 · 2023: 13 · 2022: 8 · 2021: 9 · 2020: 11 · 2019: 4 · 2018: 1
- FWCI
- 4.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancers (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Krebshilfe (70112872 / 70113144)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Electromagnetic Fields and Biological Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Microbial Inactivation Methods
- Keywords
- tumor treating fields, CaV1.2 channels, voltage-gated calcium channels, glioblastoma, calcium signaling, cell cycle arrest, mitochondrial membrane potential, clonogenic survival, benidipine, calcium channel blockers
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