Real-Time Monitoring of the Effect of Tumour-Treating Fields on Cell Division Using Live-Cell Imaging
The effects of electric fields (EFs) on various cell types have been thoroughly studied, and exhibit a well-known regulatory effect on cell processes, implicating their usage in several medical applications. While the specific effect exerted on cells is highly parameter-dependent, the majority of pa...
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MDPI AG
2022-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/17/2712 |
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| author | Hoa T. Le Michael Staelens Davide Lazzari Gordon Chan Jack A. Tuszyński |
| author_facet | Hoa T. Le Michael Staelens Davide Lazzari Gordon Chan Jack A. Tuszyński |
| author_sort | Hoa T. Le |
| collection | DOAJ |
| description | The effects of electric fields (EFs) on various cell types have been thoroughly studied, and exhibit a well-known regulatory effect on cell processes, implicating their usage in several medical applications. While the specific effect exerted on cells is highly parameter-dependent, the majority of past research has focused primarily on low-frequency alternating fields (<1 kHz) and high-frequency fields (in the order of MHz). However, in recent years, low-intensity (1–3 V/cm) alternating EFs with intermediate frequencies (100–500 kHz) have been of topical interest as clinical treatments for cancerous tumours through their disruption of cell division and the mitotic spindle, which can lead to cell death. These aptly named tumour-treating fields (TTFields) have been approved by the FDA as a treatment modality for several cancers, such as malignant pleural mesothelioma and glioblastoma multiforme, demonstrating remarkable efficacy and a high safety profile. In this work, we report the results of in vitro experiments with HeLa and MCF-10A cells exposed to TTFields for 18 h, imaged in real time using live-cell imaging. Both studied cell lines were exposed to 100 kHz TTFields with a 1-1 duty cycle, which resulted in significant mitotic and cytokinetic arrest. In the experiments with HeLa cells, the effects of the TTFields’ frequency (100 kHz vs. 200 kHz) and duty cycle (1-1 vs. 1-0) were also investigated. Notably, the anti-mitotic effect was stronger in the HeLa cells treated with 100 kHz TTFields. Additionally, it was found that single and two-directional TTFields (oriented orthogonally) exhibit a similar inhibitory effect on HeLa cell division. These results provide real-time evidence of the profound ability of TTFields to hinder the process of cell division by significantly delaying both the mitosis and cytokinesis phases of the cell cycle. |
| first_indexed | 2024-03-10T01:57:19Z |
| format | Article |
| id | doaj.art-de527b6fd7894af6b7783afc6867ded6 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T01:57:19Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-de527b6fd7894af6b7783afc6867ded62023-11-23T12:55:41ZengMDPI AGCells2073-44092022-08-011117271210.3390/cells11172712Real-Time Monitoring of the Effect of Tumour-Treating Fields on Cell Division Using Live-Cell ImagingHoa T. Le0Michael Staelens1Davide Lazzari2Gordon Chan3Jack A. Tuszyński4Department of Medical Microbiology & Immunology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2E1, CanadaDepartment of Physics, Faculty of Science, University of Alberta, Edmonton, AB T6G 2E1, CanadaDipartimento di Ingegneria Meccanica e Aerospaziale (DIMEAS), Politecnico di Torino, 10129 Turin, ItalyDepartment of Oncology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 1Z2, CanadaDepartment of Physics, Faculty of Science, University of Alberta, Edmonton, AB T6G 2E1, CanadaThe effects of electric fields (EFs) on various cell types have been thoroughly studied, and exhibit a well-known regulatory effect on cell processes, implicating their usage in several medical applications. While the specific effect exerted on cells is highly parameter-dependent, the majority of past research has focused primarily on low-frequency alternating fields (<1 kHz) and high-frequency fields (in the order of MHz). However, in recent years, low-intensity (1–3 V/cm) alternating EFs with intermediate frequencies (100–500 kHz) have been of topical interest as clinical treatments for cancerous tumours through their disruption of cell division and the mitotic spindle, which can lead to cell death. These aptly named tumour-treating fields (TTFields) have been approved by the FDA as a treatment modality for several cancers, such as malignant pleural mesothelioma and glioblastoma multiforme, demonstrating remarkable efficacy and a high safety profile. In this work, we report the results of in vitro experiments with HeLa and MCF-10A cells exposed to TTFields for 18 h, imaged in real time using live-cell imaging. Both studied cell lines were exposed to 100 kHz TTFields with a 1-1 duty cycle, which resulted in significant mitotic and cytokinetic arrest. In the experiments with HeLa cells, the effects of the TTFields’ frequency (100 kHz vs. 200 kHz) and duty cycle (1-1 vs. 1-0) were also investigated. Notably, the anti-mitotic effect was stronger in the HeLa cells treated with 100 kHz TTFields. Additionally, it was found that single and two-directional TTFields (oriented orthogonally) exhibit a similar inhibitory effect on HeLa cell division. These results provide real-time evidence of the profound ability of TTFields to hinder the process of cell division by significantly delaying both the mitosis and cytokinesis phases of the cell cycle.https://www.mdpi.com/2073-4409/11/17/2712oncologyelectromagnetic fieldsnon-invasive therapieshuman cervical carcinoma cellshuman breast epithelial cellsthymidine block |
| spellingShingle | Hoa T. Le Michael Staelens Davide Lazzari Gordon Chan Jack A. Tuszyński Real-Time Monitoring of the Effect of Tumour-Treating Fields on Cell Division Using Live-Cell Imaging Cells oncology electromagnetic fields non-invasive therapies human cervical carcinoma cells human breast epithelial cells thymidine block |
| title | Real-Time Monitoring of the Effect of Tumour-Treating Fields on Cell Division Using Live-Cell Imaging |
| title_full | Real-Time Monitoring of the Effect of Tumour-Treating Fields on Cell Division Using Live-Cell Imaging |
| title_fullStr | Real-Time Monitoring of the Effect of Tumour-Treating Fields on Cell Division Using Live-Cell Imaging |
| title_full_unstemmed | Real-Time Monitoring of the Effect of Tumour-Treating Fields on Cell Division Using Live-Cell Imaging |
| title_short | Real-Time Monitoring of the Effect of Tumour-Treating Fields on Cell Division Using Live-Cell Imaging |
| title_sort | real time monitoring of the effect of tumour treating fields on cell division using live cell imaging |
| topic | oncology electromagnetic fields non-invasive therapies human cervical carcinoma cells human breast epithelial cells thymidine block |
| url | https://www.mdpi.com/2073-4409/11/17/2712 |
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